1-[(3RS,4RS)-1-Benzyl-4-methyl-piperi-din-3-yl]-1,6-dihydro-imidazo[4,5-d]pyrrolo-[2,3-b]pyridine hemihydrate.

The benzyl residue in the title compound, C(21)H(23)N(5)·0.5H(2)O, is oriented at a dihedral angle of 83.8 (3)° towards the 1,6-dihydro-imidazo[4,5-d]pyrrolo-[2,3-b]pyridine system. The piperidine ring adopts a chair conformation with the cis substituents displaying a torsion angle of -45.91 (16)°. In the crystal, mol-ecules are accumulated as racemic dimers by two inter-molecular hydrogen bonds between the pyrrolo-pyridine systems. Another hydrogen bond is formed between the imidazole ring and the cocrystallized water mol-ecule, which is located on a twofold rotation axis.

Related literature

For biological details on Janus protein tyrosine kinases, see: Kulagowski et al. (2012 ▶). For synthetic details, see: Bajwa et al. (2006 ▶).

Experimental

Crystal data

C21H23N5·0.5H2O

M = 354.45

Monoclinic,

a = 17.3606 (19) Å

b = 10.0422 (10) Å

c = 22.995 (2) Å

β = 100.965 (3)°

V = 3935.8 (7) Å3

Z = 8

Mo Kα radiation

μ = 0.08 mm−1

T = 173 K

0.50 × 0.27 × 0.20 mm

Data collection

Bruker APEXII diffractometer

22115 measured reflections

4571 independent reflections

3504 reflections with I > 2σ(I)

R int = 0.040

Standard reflections: ?

Refinement

R[F 2 > 2σ(F 2)] = 0.045

wR(F 2) = 0.109

S = 1.03

4571 reflections

240 parameters

H-atom parameters constrained

Δρmax = 0.37 e Å−3

Δρmin = −0.30 e Å−3

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812039980/bt6840sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812039980/bt6840Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812039980/bt6840Isup3.cml

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

C21H23N5·0.5H2O	F(000) = 1512
Mr = 354.45	Dx = 1.196 Mg m−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 4892 reflections
a = 17.3606 (19) Å	θ = 2.4–26.7°
b = 10.0422 (10) Å	µ = 0.08 mm−1
c = 22.995 (2) Å	T = 173 K
β = 100.965 (3)°	Block, colourless
V = 3935.8 (7) Å3	0.50 × 0.27 × 0.20 mm
Z = 8

Bruker APEXII diffractometer	3504 reflections with I > 2σ(I)
Radiation source: sealed Tube	Rint = 0.040
Graphite monochromator	θmax = 27.7°, θmin = 1.8°
CCD scan	h = −21→22
22115 measured reflections	k = −13→12
4571 independent reflections	l = −30→30

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.109	H-atom parameters constrained
S = 1.03	w = 1/[σ2(Fo2) + (0.0401P)2 + 2.9543P] where P = (Fo2 + 2Fc2)/3
4571 reflections	(Δ/σ)max < 0.001
240 parameters	Δρmax = 0.37 e Å−3
0 restraints	Δρmin = −0.30 e Å−3

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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
N1	0.23581 (6)	0.09700 (11)	0.24008 (5)	0.0258 (3)
C2	0.30258 (8)	0.02507 (14)	0.26224 (7)	0.0293 (3)
H2	0.3148	−0.0059	0.3020	0.035*
N3	0.34774 (7)	0.00328 (13)	0.22344 (5)	0.0310 (3)
C4	0.30842 (8)	0.06430 (14)	0.17183 (6)	0.0288 (3)
C5	0.33093 (9)	0.07650 (15)	0.11641 (7)	0.0338 (3)
H5	0.3783	0.0356	0.1108	0.041*
N6	0.28808 (8)	0.14347 (13)	0.07164 (6)	0.0362 (3)
C7	0.22083 (9)	0.19640 (14)	0.08238 (7)	0.0319 (3)
N8	0.16809 (8)	0.26560 (13)	0.04086 (6)	0.0373 (3)
H8	0.1745	0.2858	0.0004	0.056*
C9	0.10645 (10)	0.30373 (15)	0.06626 (7)	0.0375 (4)
H9	0.0625	0.3533	0.0466	0.045*
C10	0.11658 (9)	0.26095 (15)	0.12371 (7)	0.0328 (3)
H10	0.0820	0.2746	0.1506	0.039*
C11	0.18991 (8)	0.19139 (14)	0.13518 (6)	0.0285 (3)
C12	0.23855 (8)	0.12243 (13)	0.18146 (6)	0.0261 (3)
C13	0.17177 (8)	0.13850 (14)	0.27023 (6)	0.0257 (3)
H13	0.1425	0.2113	0.2458	0.031*
C14	0.11248 (8)	0.02574 (14)	0.27341 (6)	0.0284 (3)
H14	0.0641	0.0683	0.2826	0.034*
C15	0.14310 (8)	−0.06998 (14)	0.32409 (7)	0.0323 (3)
H15A	0.1007	−0.1323	0.3291	0.039*
H15B	0.1867	−0.1230	0.3139	0.039*
C16	0.17175 (8)	0.00276 (15)	0.38202 (7)	0.0320 (3)
H16A	0.1278	0.0524	0.3936	0.038*
H16B	0.1915	−0.0623	0.4137	0.038*
N17	0.23465 (7)	0.09550 (12)	0.37510 (5)	0.0275 (3)
C18	0.20358 (8)	0.19706 (14)	0.33118 (6)	0.0273 (3)
H18A	0.2457	0.2614	0.3279	0.033*
H18B	0.1610	0.2463	0.3450	0.033*
C19	0.08819 (9)	−0.04706 (17)	0.21443 (7)	0.0379 (4)
H19A	0.0685	0.0175	0.1832	0.057*
H19B	0.0468	−0.1116	0.2176	0.057*
H19C	0.1337	−0.0938	0.2047	0.057*
C20	0.26827 (9)	0.15779 (16)	0.43189 (6)	0.0331 (3)
H20A	0.2786	0.0881	0.4629	0.040*
H20B	0.2296	0.2207	0.4429	0.040*
C21	0.34369 (8)	0.23169 (14)	0.43017 (6)	0.0278 (3)
C22	0.35253 (9)	0.36471 (15)	0.44601 (6)	0.0312 (3)
H22	0.3098	0.4116	0.4567	0.037*
C23	0.42287 (9)	0.43037 (16)	0.44643 (7)	0.0373 (4)
H23	0.4283	0.5213	0.4578	0.045*
C24	0.48489 (9)	0.36375 (18)	0.43038 (7)	0.0412 (4)
H24	0.5333	0.4084	0.4312	0.049*
C25	0.47669 (10)	0.23215 (19)	0.41312 (8)	0.0445 (4)
H25	0.5191	0.1866	0.4013	0.053*
C26	0.40644 (9)	0.16630 (16)	0.41310 (7)	0.0381 (4)
H26	0.4011	0.0756	0.4013	0.046*
O1W	0.5000	−0.1491 (2)	0.2500	0.0825 (8)
H1W	0.4569	−0.0982	0.2336	0.124*

	U11	U22	U33	U12	U13	U23
N1	0.0244 (6)	0.0261 (6)	0.0264 (6)	−0.0000 (5)	0.0040 (5)	−0.0001 (5)
C2	0.0261 (7)	0.0294 (7)	0.0314 (7)	0.0011 (6)	0.0028 (6)	−0.0000 (6)
N3	0.0260 (6)	0.0326 (7)	0.0344 (7)	−0.0007 (5)	0.0059 (5)	−0.0011 (5)
C4	0.0275 (7)	0.0262 (7)	0.0330 (8)	−0.0046 (6)	0.0066 (6)	−0.0010 (6)
C5	0.0321 (8)	0.0326 (8)	0.0389 (8)	−0.0052 (6)	0.0122 (6)	−0.0010 (7)
N6	0.0409 (7)	0.0353 (7)	0.0346 (7)	−0.0064 (6)	0.0126 (6)	0.0017 (6)
C7	0.0394 (8)	0.0260 (7)	0.0304 (8)	−0.0073 (6)	0.0068 (6)	0.0007 (6)
N8	0.0489 (8)	0.0342 (7)	0.0283 (7)	−0.0014 (6)	0.0063 (6)	0.0048 (6)
C9	0.0451 (9)	0.0298 (8)	0.0353 (8)	0.0034 (7)	0.0020 (7)	0.0020 (7)
C10	0.0387 (8)	0.0282 (7)	0.0304 (8)	0.0016 (6)	0.0040 (6)	−0.0004 (6)
C11	0.0330 (7)	0.0233 (7)	0.0288 (7)	−0.0052 (6)	0.0046 (6)	−0.0014 (6)
C12	0.0290 (7)	0.0220 (6)	0.0274 (7)	−0.0062 (5)	0.0056 (5)	−0.0018 (6)
C13	0.0252 (7)	0.0242 (7)	0.0274 (7)	0.0035 (5)	0.0042 (5)	−0.0005 (6)
C14	0.0215 (7)	0.0316 (7)	0.0320 (8)	0.0001 (5)	0.0048 (6)	−0.0044 (6)
C15	0.0279 (7)	0.0256 (7)	0.0424 (9)	−0.0045 (6)	0.0044 (6)	0.0001 (6)
C16	0.0308 (7)	0.0300 (7)	0.0346 (8)	−0.0056 (6)	0.0048 (6)	0.0059 (6)
N17	0.0298 (6)	0.0267 (6)	0.0251 (6)	−0.0058 (5)	0.0027 (5)	0.0018 (5)
C18	0.0308 (7)	0.0233 (7)	0.0281 (7)	−0.0009 (6)	0.0060 (6)	−0.0008 (6)
C19	0.0304 (8)	0.0443 (9)	0.0393 (9)	−0.0065 (7)	0.0069 (6)	−0.0123 (7)
C20	0.0352 (8)	0.0391 (8)	0.0251 (7)	−0.0084 (6)	0.0062 (6)	0.0003 (6)
C21	0.0301 (7)	0.0305 (7)	0.0214 (7)	−0.0027 (6)	0.0013 (5)	0.0016 (6)
C22	0.0343 (8)	0.0326 (8)	0.0262 (7)	−0.0000 (6)	0.0045 (6)	−0.0008 (6)
C23	0.0451 (9)	0.0312 (8)	0.0327 (8)	−0.0095 (7)	0.0003 (7)	0.0007 (7)
C24	0.0325 (8)	0.0513 (10)	0.0379 (9)	−0.0133 (7)	0.0018 (7)	0.0072 (8)
C25	0.0306 (8)	0.0537 (11)	0.0496 (10)	0.0062 (7)	0.0087 (7)	0.0011 (8)
C26	0.0371 (8)	0.0315 (8)	0.0447 (9)	0.0015 (6)	0.0052 (7)	−0.0030 (7)
O1W	0.0391 (11)	0.0429 (11)	0.158 (2)	0.000	0.0001 (12)	0.000

N1—C2	1.3786 (18)	C15—H15A	0.9900
N1—C12	1.3815 (18)	C15—H15B	0.9900
N1—C13	1.4777 (17)	C16—N17	1.4667 (17)
C2—N3	1.3132 (18)	C16—H16A	0.9900
C2—H2	0.9500	C16—H16B	0.9900
N3—C4	1.3936 (19)	N17—C18	1.4642 (18)
C4—C12	1.401 (2)	N17—C20	1.4654 (18)
C4—C5	1.407 (2)	C18—H18A	0.9900
C5—N6	1.332 (2)	C18—H18B	0.9900
C5—H5	0.9500	C19—H19A	0.9800
N6—C7	1.348 (2)	C19—H19B	0.9800
C7—N8	1.378 (2)	C19—H19C	0.9800
C7—C11	1.419 (2)	C20—C21	1.512 (2)
N8—C9	1.368 (2)	C20—H20A	0.9900
N8—H8	0.9793	C20—H20B	0.9900
C9—C10	1.368 (2)	C21—C22	1.385 (2)
C9—H9	0.9500	C21—C26	1.391 (2)
C10—C11	1.432 (2)	C22—C23	1.386 (2)
C10—H10	0.9500	C22—H22	0.9500
C11—C12	1.408 (2)	C23—C24	1.376 (2)
C13—C18	1.5234 (19)	C23—H23	0.9500
C13—C14	1.5414 (19)	C24—C25	1.379 (3)
C13—H13	1.0000	C24—H24	0.9500
C14—C15	1.526 (2)	C25—C26	1.387 (2)
C14—C19	1.528 (2)	C25—H25	0.9500
C14—H14	1.0000	C26—H26	0.9500
C15—C16	1.518 (2)	O1W—H1W	0.9253
C2—N1—C12	105.96 (11)	C14—C15—H15B	109.2
C2—N1—C13	128.98 (12)	H15A—C15—H15B	107.9
C12—N1—C13	125.05 (11)	N17—C16—C15	109.69 (12)
N3—C2—N1	113.88 (13)	N17—C16—H16A	109.7
N3—C2—H2	123.1	C15—C16—H16A	109.7
N1—C2—H2	123.1	N17—C16—H16B	109.7
C2—N3—C4	104.26 (12)	C15—C16—H16B	109.7
N3—C4—C12	110.30 (12)	H16A—C16—H16B	108.2
N3—C4—C5	129.35 (13)	C18—N17—C20	110.45 (11)
C12—C4—C5	120.31 (13)	C18—N17—C16	109.44 (11)
N6—C5—C4	122.23 (14)	C20—N17—C16	110.67 (11)
N6—C5—H5	118.9	N17—C18—C13	112.78 (11)
C4—C5—H5	118.9	N17—C18—H18A	109.0
C5—N6—C7	115.68 (13)	C13—C18—H18A	109.0
N6—C7—N8	123.80 (13)	N17—C18—H18B	109.0
N6—C7—C11	128.67 (14)	C13—C18—H18B	109.0
N8—C7—C11	107.52 (13)	H18A—C18—H18B	107.8
C9—N8—C7	108.42 (13)	C14—C19—H19A	109.5
C9—N8—H8	126.0	C14—C19—H19B	109.5
C7—N8—H8	125.6	H19A—C19—H19B	109.5
N8—C9—C10	110.92 (14)	C14—C19—H19C	109.5
N8—C9—H9	124.5	H19A—C19—H19C	109.5
C10—C9—H9	124.5	H19B—C19—H19C	109.5
C9—C10—C11	106.11 (14)	N17—C20—C21	112.72 (11)
C9—C10—H10	126.9	N17—C20—H20A	109.0
C11—C10—H10	126.9	C21—C20—H20A	109.0
C12—C11—C7	113.22 (13)	N17—C20—H20B	109.0
C12—C11—C10	139.75 (14)	C21—C20—H20B	109.0
C7—C11—C10	107.03 (13)	H20A—C20—H20B	107.8
N1—C12—C4	105.59 (12)	C22—C21—C26	118.41 (14)
N1—C12—C11	134.53 (13)	C22—C21—C20	121.30 (13)
C4—C12—C11	119.86 (13)	C26—C21—C20	120.28 (13)
N1—C13—C18	111.55 (11)	C21—C22—C23	120.92 (14)
N1—C13—C14	112.57 (11)	C21—C22—H22	119.5
C18—C13—C14	111.61 (11)	C23—C22—H22	119.5
N1—C13—H13	106.9	C24—C23—C22	120.00 (15)
C18—C13—H13	106.9	C24—C23—H23	120.0
C14—C13—H13	106.9	C22—C23—H23	120.0
C15—C14—C19	111.95 (12)	C23—C24—C25	119.98 (15)
C15—C14—C13	111.12 (11)	C23—C24—H24	120.0
C19—C14—C13	112.55 (12)	C25—C24—H24	120.0
C15—C14—H14	106.9	C24—C25—C26	119.96 (16)
C19—C14—H14	106.9	C24—C25—H25	120.0
C13—C14—H14	106.9	C26—C25—H25	120.0
C16—C15—C14	112.05 (12)	C25—C26—C21	120.70 (15)
C16—C15—H15A	109.2	C25—C26—H26	119.6
C14—C15—H15A	109.2	C21—C26—H26	119.6
C16—C15—H15B	109.2
C12—N1—C2—N3	0.50 (16)	C10—C11—C12—C4	178.39 (16)
C13—N1—C2—N3	179.23 (12)	C2—N1—C13—C18	46.14 (18)
N1—C2—N3—C4	−0.21 (16)	C12—N1—C13—C18	−135.35 (13)
C2—N3—C4—C12	−0.15 (15)	C2—N1—C13—C14	−80.23 (17)
C2—N3—C4—C5	177.61 (15)	C12—N1—C13—C14	98.28 (15)
N3—C4—C5—N6	−176.99 (14)	N1—C13—C14—C15	80.55 (14)
C12—C4—C5—N6	0.6 (2)	C18—C13—C14—C15	−45.79 (15)
C4—C5—N6—C7	−1.4 (2)	N1—C13—C14—C19	−45.91 (16)
C5—N6—C7—N8	−178.11 (14)	C18—C13—C14—C19	−172.24 (12)
C5—N6—C7—C11	0.6 (2)	C19—C14—C15—C16	176.63 (12)
N6—C7—N8—C9	179.33 (14)	C13—C14—C15—C16	49.84 (15)
C11—C7—N8—C9	0.35 (16)	C14—C15—C16—N17	−58.88 (15)
C7—N8—C9—C10	−0.34 (18)	C15—C16—N17—C18	63.33 (15)
N8—C9—C10—C11	0.18 (18)	C15—C16—N17—C20	−174.72 (12)
N6—C7—C11—C12	0.9 (2)	C20—N17—C18—C13	176.90 (11)
N8—C7—C11—C12	179.84 (12)	C16—N17—C18—C13	−61.02 (14)
N6—C7—C11—C10	−179.16 (14)	N1—C13—C18—N17	−74.69 (14)
N8—C7—C11—C10	−0.24 (16)	C14—C13—C18—N17	52.20 (15)
C9—C10—C11—C12	179.93 (17)	C18—N17—C20—C21	−70.56 (15)
C9—C10—C11—C7	0.04 (16)	C16—N17—C20—C21	168.08 (12)
C2—N1—C12—C4	−0.54 (14)	N17—C20—C21—C22	124.87 (14)
C13—N1—C12—C4	−179.34 (12)	N17—C20—C21—C26	−55.85 (18)
C2—N1—C12—C11	−178.93 (15)	C26—C21—C22—C23	−1.7 (2)
C13—N1—C12—C11	2.3 (2)	C20—C21—C22—C23	177.56 (13)
N3—C4—C12—N1	0.44 (15)	C21—C22—C23—C24	0.7 (2)
C5—C4—C12—N1	−177.55 (12)	C22—C23—C24—C25	0.9 (2)
N3—C4—C12—C11	179.12 (12)	C23—C24—C25—C26	−1.3 (3)
C5—C4—C12—C11	1.1 (2)	C24—C25—C26—C21	0.2 (3)
C7—C11—C12—N1	176.48 (14)	C22—C21—C26—C25	1.3 (2)
C10—C11—C12—N1	−3.4 (3)	C20—C21—C26—C25	−178.01 (14)
C7—C11—C12—C4	−1.73 (18)

D—H···A	D—H	H···A	D···A	D—H···A
N8—H8···N6i	0.98	2.02	2.9757 (18)	165
O1W—H1W···N3	0.93	2.13	3.0148 (16)	161

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N8—H8⋯N6i	0.98	2.02	2.9757 (18)	165
O1W—H1W⋯N3	0.93	2.13	3.0148 (16)	161

Symmetry code: (i) .