Methyl 2-acetamido-2-(4-hy-droxy-2-methyl-1,3-dioxo-1,2,3,4-tetra-hydro-isoquinolin-4-yl)-4-methyl-penta-noate.

In the isoquinoline ring system of the title mol-ecule, C(19)H(24)N(2)O(6), the N-heterocyclic ring is in a half-boat conformation. The mol-ecular structure is stabilized by an intra-molecular O-H⋯O hydrogen bond, which generates an S(7) ring motif. In the crystal, mol-ecules are linked via inter-molecular bifurcated N-H⋯(O,O) and weak C-H⋯O hydrogen bonds into a three-dimensional network.

Related literature

For general background to and the potential biological activity of title compound, see: Yu et al. (2010 ▶); Huang et al. (2011 ▶); Rao et al. (1995 ▶); Nagamitsu et al. (1996 ▶); Evans & Weber (1986 ▶); Heimgartner (1991 ▶); Rando (1975 ▶); Griesbeck et al. (2003 ▶); Zhang et al. (2004 ▶); Wang et al. (2010 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶). For standard bond-length data, see: Allen et al. (1987 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For related structures, see: Fun et al. (2011a ▶,b ▶,c ▶,d ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C19H24N2O6

M = 376.40

Monoclinic,

a = 17.8256 (15) Å

b = 8.7584 (6) Å

c = 11.9182 (8) Å

β = 100.404 (5)°

V = 1830.1 (2) Å3

Z = 4

Cu Kα radiation

μ = 0.85 mm−1

T = 100 K

0.50 × 0.15 × 0.15 mm

Data collection

Bruker APEX DUO CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T min = 0.678, T max = 0.883

18268 measured reflections

2713 independent reflections

2673 reflections with I > 2σ(I)

R int = 0.033

Refinement

R[F 2 > 2σ(F 2)] = 0.024

wR(F 2) = 0.059

S = 1.05

2713 reflections

257 parameters

2 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.11 e Å−3

Δρmin = −0.14 e Å−3

Absolute structure: Flack (1983 ▶), 1204 Friedel pairs

Flack parameter: 0.05 (13)

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811022999/lh5262sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811022999/lh5262Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811022999/lh5262Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C19H24N2O6	F(000) = 800
Mr = 376.40	Dx = 1.366 Mg m−3
Monoclinic, Cc	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: C -2yc	Cell parameters from 9888 reflections
a = 17.8256 (15) Å	θ = 5.1–64.2°
b = 8.7584 (6) Å	µ = 0.85 mm−1
c = 11.9182 (8) Å	T = 100 K
β = 100.404 (5)°	Needle, colourless
V = 1830.1 (2) Å3	0.50 × 0.15 × 0.15 mm
Z = 4

Bruker APEX DUO CCD area-detector diffractometer	2713 independent reflections
Radiation source: fine-focus sealed tube	2673 reflections with I > 2σ(I)
graphite	Rint = 0.033
φ and ω scans	θmax = 64.7°, θmin = 5.1°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −20→20
Tmin = 0.678, Tmax = 0.883	k = −9→10
18268 measured reflections	l = −12→13

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.024	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.059	w = 1/[σ2(Fo2) + (0.0319P)2 + 0.7184P] where P = (Fo2 + 2Fc2)/3
S = 1.05	(Δ/σ)max < 0.001
2713 reflections	Δρmax = 0.11 e Å−3
257 parameters	Δρmin = −0.14 e Å−3
2 restraints	Absolute structure: Flack (1983), 1204 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.05 (13)

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
O1	0.81985 (6)	0.74615 (13)	1.04040 (10)	0.0229 (3)
O2	1.05834 (6)	0.65801 (14)	0.97375 (10)	0.0302 (3)
O3	0.76692 (6)	0.48621 (12)	0.94001 (10)	0.0204 (2)
O4	0.91523 (6)	0.77211 (12)	0.76247 (9)	0.0193 (2)
O5	0.89019 (6)	0.56633 (12)	0.65074 (9)	0.0204 (2)
O6	0.64674 (6)	0.52211 (12)	0.77471 (10)	0.0223 (3)
N1	0.93918 (7)	0.70763 (15)	1.00450 (11)	0.0206 (3)
N2	0.75643 (7)	0.51865 (14)	0.70247 (12)	0.0171 (3)
C1	0.86194 (9)	0.67556 (17)	0.99008 (14)	0.0188 (3)
C2	0.99257 (9)	0.61559 (19)	0.96548 (14)	0.0222 (4)
C3	0.96586 (9)	0.46387 (18)	0.91865 (14)	0.0200 (3)
C4	1.02036 (9)	0.3555 (2)	0.90385 (14)	0.0253 (4)
H4A	1.0719	0.3803	0.9194	0.030*
C5	0.99735 (10)	0.2104 (2)	0.86574 (15)	0.0285 (4)
H5A	1.0334	0.1376	0.8550	0.034*
C6	0.92023 (10)	0.17437 (19)	0.84364 (15)	0.0259 (4)
H6A	0.9049	0.0765	0.8192	0.031*
C7	0.86576 (9)	0.28210 (18)	0.85750 (14)	0.0217 (3)
H7A	0.8143	0.2565	0.8424	0.026*
C8	0.88811 (8)	0.42821 (18)	0.89389 (13)	0.0181 (3)
C9	0.82982 (8)	0.55120 (17)	0.90207 (14)	0.0174 (3)
C10	0.80278 (8)	0.62935 (17)	0.77805 (14)	0.0167 (3)
C11	0.76008 (9)	0.78137 (17)	0.78789 (13)	0.0180 (3)
H11A	0.7260	0.7664	0.8419	0.022*
H11B	0.7974	0.8574	0.8201	0.022*
C12	0.71318 (9)	0.84730 (17)	0.67768 (15)	0.0217 (3)
H12A	0.6734	0.7732	0.6477	0.026*
C13	0.75969 (10)	0.8792 (2)	0.58470 (15)	0.0285 (4)
H13A	0.7803	0.7852	0.5620	0.043*
H13B	0.8006	0.9479	0.6135	0.043*
H13C	0.7274	0.9246	0.5201	0.043*
C14	0.67409 (10)	0.9933 (2)	0.70714 (17)	0.0306 (4)
H14A	0.6414	1.0315	0.6401	0.046*
H14B	0.7120	1.0686	0.7352	0.046*
H14C	0.6443	0.9716	0.7647	0.046*
C15	0.87344 (8)	0.65099 (17)	0.72155 (14)	0.0165 (3)
C16	0.98383 (9)	0.79217 (19)	0.71419 (15)	0.0230 (4)
H16A	1.0110	0.8807	0.7472	0.035*
H16B	0.9701	0.8053	0.6331	0.035*
H16C	1.0158	0.7037	0.7304	0.035*
C17	0.68252 (8)	0.48575 (17)	0.69911 (14)	0.0179 (3)
C18	0.64504 (9)	0.40140 (19)	0.59393 (15)	0.0248 (4)
H18A	0.6056	0.3365	0.6124	0.037*
H18B	0.6824	0.3404	0.5657	0.037*
H18C	0.6232	0.4734	0.5365	0.037*
C19	0.96743 (10)	0.84909 (19)	1.06333 (17)	0.0300 (4)
H19A	0.9273	0.8958	1.0952	0.045*
H19B	0.9839	0.9179	1.0100	0.045*
H19C	1.0096	0.8261	1.1233	0.045*
H1N2	0.7798 (11)	0.479 (2)	0.6459 (18)	0.025 (5)*
H1O3	0.7237 (13)	0.510 (2)	0.8986 (18)	0.037 (6)*

	U11	U22	U33	U12	U13	U23
O1	0.0255 (6)	0.0248 (6)	0.0184 (7)	0.0040 (4)	0.0040 (5)	−0.0020 (5)
O2	0.0178 (6)	0.0408 (7)	0.0299 (8)	−0.0067 (5)	−0.0013 (5)	0.0021 (6)
O3	0.0173 (5)	0.0267 (6)	0.0173 (7)	−0.0020 (4)	0.0036 (5)	0.0027 (5)
O4	0.0171 (5)	0.0208 (5)	0.0201 (7)	−0.0039 (4)	0.0033 (4)	−0.0013 (5)
O5	0.0191 (5)	0.0237 (5)	0.0188 (7)	−0.0013 (4)	0.0046 (4)	−0.0021 (5)
O6	0.0177 (5)	0.0279 (6)	0.0215 (7)	−0.0011 (4)	0.0045 (5)	−0.0014 (5)
N1	0.0220 (7)	0.0223 (7)	0.0162 (8)	−0.0040 (5)	−0.0003 (5)	0.0005 (6)
N2	0.0163 (7)	0.0188 (7)	0.0161 (8)	−0.0006 (5)	0.0026 (6)	−0.0022 (5)
C1	0.0221 (8)	0.0190 (7)	0.0143 (9)	0.0005 (6)	0.0004 (6)	0.0044 (6)
C2	0.0195 (8)	0.0310 (9)	0.0143 (9)	−0.0008 (6)	−0.0019 (6)	0.0057 (7)
C3	0.0206 (8)	0.0281 (8)	0.0112 (9)	0.0010 (6)	0.0024 (6)	0.0038 (7)
C4	0.0210 (8)	0.0383 (10)	0.0163 (10)	0.0049 (7)	0.0027 (7)	0.0045 (7)
C5	0.0322 (10)	0.0339 (10)	0.0193 (11)	0.0139 (7)	0.0042 (7)	0.0002 (7)
C6	0.0352 (10)	0.0242 (9)	0.0168 (10)	0.0055 (7)	0.0009 (7)	0.0007 (7)
C7	0.0248 (8)	0.0246 (8)	0.0151 (9)	0.0009 (7)	0.0021 (6)	−0.0002 (7)
C8	0.0210 (8)	0.0239 (8)	0.0095 (9)	0.0021 (6)	0.0030 (6)	0.0028 (6)
C9	0.0167 (7)	0.0204 (8)	0.0149 (9)	−0.0010 (6)	0.0025 (6)	0.0017 (6)
C10	0.0161 (7)	0.0196 (7)	0.0130 (9)	−0.0030 (6)	−0.0007 (6)	−0.0009 (6)
C11	0.0159 (7)	0.0216 (8)	0.0163 (9)	0.0001 (6)	0.0025 (6)	0.0005 (6)
C12	0.0204 (7)	0.0219 (8)	0.0207 (10)	−0.0012 (6)	−0.0015 (6)	0.0013 (7)
C13	0.0318 (9)	0.0316 (9)	0.0212 (10)	0.0051 (7)	0.0022 (7)	0.0070 (8)
C14	0.0318 (9)	0.0302 (9)	0.0280 (12)	0.0085 (7)	0.0002 (8)	0.0036 (8)
C15	0.0156 (7)	0.0191 (8)	0.0134 (9)	−0.0003 (6)	−0.0010 (6)	0.0030 (6)
C16	0.0190 (8)	0.0264 (8)	0.0238 (10)	−0.0048 (6)	0.0043 (7)	0.0010 (7)
C17	0.0165 (7)	0.0178 (7)	0.0191 (10)	−0.0003 (6)	0.0018 (6)	0.0013 (6)
C18	0.0178 (8)	0.0319 (9)	0.0241 (10)	−0.0055 (7)	0.0024 (7)	−0.0034 (8)
C19	0.0364 (10)	0.0282 (9)	0.0235 (10)	−0.0103 (7)	0.0004 (8)	−0.0038 (8)

O1—C1	1.211 (2)	C8—C9	1.512 (2)
O2—C2	1.217 (2)	C9—C10	1.621 (2)
O3—C9	1.4032 (19)	C10—C15	1.543 (2)
O3—H1O3	0.86 (2)	C10—C11	1.549 (2)
O4—C15	1.3368 (18)	C11—C12	1.537 (2)
O4—C16	1.4531 (18)	C11—H11A	0.9700
O5—C15	1.201 (2)	C11—H11B	0.9700
O6—C17	1.236 (2)	C12—C13	1.525 (3)
N1—C1	1.3851 (19)	C12—C14	1.527 (2)
N1—C2	1.390 (2)	C12—H12A	0.9800
N1—C19	1.467 (2)	C13—H13A	0.9600
N2—C17	1.3420 (19)	C13—H13B	0.9600
N2—C10	1.4715 (19)	C13—H13C	0.9600
N2—H1N2	0.92 (2)	C14—H14A	0.9600
C1—C9	1.548 (2)	C14—H14B	0.9600
C2—C3	1.486 (2)	C14—H14C	0.9600
C3—C4	1.392 (2)	C16—H16A	0.9600
C3—C8	1.399 (2)	C16—H16B	0.9600
C4—C5	1.386 (3)	C16—H16C	0.9600
C4—H4A	0.9300	C17—C18	1.504 (2)
C5—C6	1.389 (3)	C18—H18A	0.9600
C5—H5A	0.9300	C18—H18B	0.9600
C6—C7	1.385 (2)	C18—H18C	0.9600
C6—H6A	0.9300	C19—H19A	0.9600
C7—C8	1.386 (2)	C19—H19B	0.9600
C7—H7A	0.9300	C19—H19C	0.9600
C9—O3—H1O3	113.6 (14)	C10—C11—H11A	108.0
C15—O4—C16	113.89 (13)	C12—C11—H11B	108.0
C1—N1—C2	124.49 (13)	C10—C11—H11B	108.0
C1—N1—C19	118.57 (13)	H11A—C11—H11B	107.2
C2—N1—C19	116.93 (13)	C13—C12—C14	110.13 (14)
C17—N2—C10	126.82 (13)	C13—C12—C11	114.00 (13)
C17—N2—H1N2	117.8 (12)	C14—C12—C11	108.57 (14)
C10—N2—H1N2	114.8 (12)	C13—C12—H12A	108.0
O1—C1—N1	121.72 (14)	C14—C12—H12A	108.0
O1—C1—C9	120.54 (14)	C11—C12—H12A	108.0
N1—C1—C9	117.67 (13)	C12—C13—H13A	109.5
O2—C2—N1	120.25 (15)	C12—C13—H13B	109.5
O2—C2—C3	122.84 (15)	H13A—C13—H13B	109.5
N1—C2—C3	116.87 (13)	C12—C13—H13C	109.5
C4—C3—C8	120.56 (15)	H13A—C13—H13C	109.5
C4—C3—C2	118.28 (14)	H13B—C13—H13C	109.5
C8—C3—C2	121.12 (14)	C12—C14—H14A	109.5
C5—C4—C3	119.65 (16)	C12—C14—H14B	109.5
C5—C4—H4A	120.2	H14A—C14—H14B	109.5
C3—C4—H4A	120.2	C12—C14—H14C	109.5
C4—C5—C6	119.64 (16)	H14A—C14—H14C	109.5
C4—C5—H5A	120.2	H14B—C14—H14C	109.5
C6—C5—H5A	120.2	O5—C15—O4	123.60 (14)
C7—C6—C5	120.92 (16)	O5—C15—C10	123.84 (13)
C7—C6—H6A	119.5	O4—C15—C10	112.54 (13)
C5—C6—H6A	119.5	O4—C16—H16A	109.5
C6—C7—C8	119.87 (15)	O4—C16—H16B	109.5
C6—C7—H7A	120.1	H16A—C16—H16B	109.5
C8—C7—H7A	120.1	O4—C16—H16C	109.5
C7—C8—C3	119.33 (14)	H16A—C16—H16C	109.5
C7—C8—C9	121.04 (13)	H16B—C16—H16C	109.5
C3—C8—C9	119.57 (14)	O6—C17—N2	123.78 (14)
O3—C9—C8	109.28 (12)	O6—C17—C18	121.61 (13)
O3—C9—C1	106.64 (13)	N2—C17—C18	114.60 (14)
C8—C9—C1	111.74 (12)	C17—C18—H18A	109.5
O3—C9—C10	109.99 (12)	C17—C18—H18B	109.5
C8—C9—C10	109.67 (13)	H18A—C18—H18B	109.5
C1—C9—C10	109.47 (12)	C17—C18—H18C	109.5
N2—C10—C15	103.07 (12)	H18A—C18—H18C	109.5
N2—C10—C11	112.55 (12)	H18B—C18—H18C	109.5
C15—C10—C11	112.23 (12)	N1—C19—H19A	109.5
N2—C10—C9	108.76 (12)	N1—C19—H19B	109.5
C15—C10—C9	108.54 (11)	H19A—C19—H19B	109.5
C11—C10—C9	111.30 (13)	N1—C19—H19C	109.5
C12—C11—C10	117.22 (13)	H19A—C19—H19C	109.5
C12—C11—H11A	108.0	H19B—C19—H19C	109.5
C2—N1—C1—O1	168.38 (15)	O1—C1—C9—C8	−151.28 (14)
C19—N1—C1—O1	−12.6 (2)	N1—C1—C9—C8	31.84 (19)
C2—N1—C1—C9	−14.8 (2)	O1—C1—C9—C10	87.02 (17)
C19—N1—C1—C9	164.27 (14)	N1—C1—C9—C10	−89.86 (15)
C1—N1—C2—O2	174.17 (15)	C17—N2—C10—C15	−164.63 (14)
C19—N1—C2—O2	−4.9 (2)	C17—N2—C10—C11	−43.5 (2)
C1—N1—C2—C3	−8.2 (2)	C17—N2—C10—C9	80.31 (18)
C19—N1—C2—C3	172.78 (14)	O3—C9—C10—N2	−49.92 (16)
O2—C2—C3—C4	12.4 (2)	C8—C9—C10—N2	70.29 (15)
N1—C2—C3—C4	−165.20 (15)	C1—C9—C10—N2	−166.77 (12)
O2—C2—C3—C8	−169.92 (15)	O3—C9—C10—C15	−161.37 (12)
N1—C2—C3—C8	12.5 (2)	C8—C9—C10—C15	−41.16 (16)
C8—C3—C4—C5	−0.9 (2)	C1—C9—C10—C15	81.77 (14)
C2—C3—C4—C5	176.79 (16)	O3—C9—C10—C11	74.64 (15)
C3—C4—C5—C6	−0.5 (3)	C8—C9—C10—C11	−165.15 (12)
C4—C5—C6—C7	1.0 (3)	C1—C9—C10—C11	−42.22 (16)
C5—C6—C7—C8	0.0 (3)	N2—C10—C11—C12	−42.05 (18)
C6—C7—C8—C3	−1.4 (2)	C15—C10—C11—C12	73.68 (17)
C6—C7—C8—C9	175.79 (15)	C9—C10—C11—C12	−164.44 (12)
C4—C3—C8—C7	1.9 (2)	C10—C11—C12—C13	−58.65 (18)
C2—C3—C8—C7	−175.74 (15)	C10—C11—C12—C14	178.18 (13)
C4—C3—C8—C9	−175.38 (15)	C16—O4—C15—O5	−0.5 (2)
C2—C3—C8—C9	7.0 (2)	C16—O4—C15—C10	177.71 (12)
C7—C8—C9—O3	37.1 (2)	N2—C10—C15—O5	−15.55 (19)
C3—C8—C9—O3	−145.72 (14)	C11—C10—C15—O5	−136.90 (15)
C7—C8—C9—C1	154.86 (15)	C9—C10—C15—O5	99.66 (17)
C3—C8—C9—C1	−27.9 (2)	N2—C10—C15—O4	166.23 (12)
C7—C8—C9—C10	−83.55 (17)	C11—C10—C15—O4	44.89 (17)
C3—C8—C9—C10	93.64 (17)	C9—C10—C15—O4	−78.55 (14)
O1—C1—C9—O3	−31.9 (2)	C10—N2—C17—O6	−15.0 (2)
N1—C1—C9—O3	151.20 (13)	C10—N2—C17—C18	164.21 (14)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H1N2···O1i	0.92 (2)	2.511 (19)	3.3431 (17)	150.3 (15)
N2—H1N2···O3i	0.92 (2)	2.44 (2)	3.1675 (18)	135.6 (16)
O3—H1O3···O6	0.86 (2)	1.83 (2)	2.6543 (16)	160 (2)
C5—H5A···O6ii	0.93	2.59	3.469 (2)	157

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N2⋯O1i	0.92 (2)	2.511 (19)	3.3431 (17)	150.3 (15)
N2—H1N2⋯O3i	0.92 (2)	2.44 (2)	3.1675 (18)	135.6 (16)
O3—H1O3⋯O6	0.86 (2)	1.83 (2)	2.6543 (16)	160 (2)
C5—H5A⋯O6ii	0.93	2.59	3.469 (2)	157

Symmetry codes: (i) ; (ii) .