tert-Butyl N-[(3R,4R)-1-(2-cyano-acet-yl)-4-methyl-piperidin-3-yl]-N-methyl-carbamate.

The piperidine ring of the title compound, C15H25N3O3, adopts a slightly distorted chair conformation with the cis substituents displaying an N-C-C-C torsion angle of 43.0 (3)°. The cyano group (plane defined by C-C-C N atoms) is bent slightly out of the plane of the amide group by 13.3 (2)°. The carbamate group is oriented at a dihedral angle of 60.3 (5)° relative to the amide group.

Related literature

For the biological activity and structure–activity relationships of Tofacitinib {systematic name: 3-[(3R,4R)-4-methyl-3-[meth­yl(7H-pyrrolo­[2,3-d]pyrimidin-4-yl)amino]­pip­eridin-1-yl]-3-oxo­propane­nitrile} derivatives, see: Changelian et al. (2003 ▶); Flanagan et al. (2010 ▶); Zerbini & Lomonte (2012 ▶). For details of the synthesis, see: Babu et al. (2010 ▶).

Experimental

Crystal data

C15H25N3O3

M = 295.38

Monoclinic,

a = 7.1786 (11) Å

b = 7.3213 (10) Å

c = 16.042 (2) Å

β = 102.196 (4)°

V = 824.1 (2) Å3

Z = 2

Mo Kα radiation

μ = 0.08 mm−1

T = 173 K

0.60 × 0.35 × 0.10 mm

Data collection

Bruker SMART APEXII diffractometer

5061 measured reflections

2115 independent reflections

1818 reflections with I > 2σ(I)

R int = 0.031

Refinement

R[F 2 > 2σ(F 2)] = 0.038

wR(F 2) = 0.101

S = 1.03

2115 reflections

195 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.24 e Å−3

Δρmin = −0.17 e Å−3

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; 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.

Click here for additional data file.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813013512/nc2311sup1.cif

Click here for additional data file.

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813013512/nc2311Isup2.hkl

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536813013512/nc2311Isup3.cml

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

C15H25N3O3	F(000) = 320
Mr = 295.38	Dx = 1.190 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 1671 reflections
a = 7.1786 (11) Å	θ = 2.6–27.7°
b = 7.3213 (10) Å	µ = 0.08 mm−1
c = 16.042 (2) Å	T = 173 K
β = 102.196 (4)°	Block, colourless
V = 824.1 (2) Å3	0.60 × 0.35 × 0.10 mm
Z = 2

Bruker SMART APEXII diffractometer	1818 reflections with I > 2σ(I)
Radiation source: sealed Tube	Rint = 0.031
Graphite monochromator	θmax = 27.8°, θmin = 2.6°
CCD scan	h = −8→9
5061 measured reflections	k = −9→9
2115 independent reflections	l = −19→21

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)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.101	H-atom parameters constrained
S = 1.03	w = 1/[σ2(Fo2) + (0.0542P)2 + 0.0849P] where P = (Fo2 + 2Fc2)/3
2115 reflections	(Δ/σ)max = 0.001
195 parameters	Δρmax = 0.24 e Å−3
1 restraint	Δρmin = −0.17 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
C1	0.4456 (3)	0.3404 (3)	0.18701 (13)	0.0302 (4)
H1	0.4716	0.2110	0.1731	0.036*
C2	0.6397 (3)	0.4395 (4)	0.20174 (18)	0.0405 (6)
H2	0.7050	0.3945	0.1564	0.049*
C3	0.6252 (3)	0.6475 (3)	0.19155 (17)	0.0399 (6)
H3A	0.5813	0.7008	0.2408	0.048*
H3B	0.7528	0.6983	0.1911	0.048*
C4	0.4877 (3)	0.7001 (3)	0.10969 (16)	0.0395 (5)
H4A	0.4737	0.8346	0.1066	0.047*
H4B	0.5387	0.6592	0.0601	0.047*
N5	0.3008 (3)	0.6153 (3)	0.10671 (12)	0.0312 (4)
C6	0.3066 (3)	0.4151 (3)	0.10847 (14)	0.0330 (5)
H6A	0.3449	0.3702	0.0563	0.040*
H6B	0.1772	0.3677	0.1081	0.040*
N7	0.3602 (2)	0.3322 (2)	0.26269 (11)	0.0285 (4)
C8	0.2959 (4)	0.4987 (3)	0.29674 (17)	0.0402 (6)
H8A	0.3926	0.5941	0.2989	0.060*
H8B	0.2757	0.4757	0.3544	0.060*
H8C	0.1760	0.5388	0.2599	0.060*
C9	0.3408 (3)	0.1672 (3)	0.29731 (13)	0.0290 (4)
O10	0.3892 (2)	0.0216 (2)	0.27102 (10)	0.0394 (4)
O11	0.2571 (2)	0.1828 (2)	0.36532 (10)	0.0372 (4)
C12	0.2052 (3)	0.0207 (3)	0.40890 (14)	0.0375 (5)
C13	0.3833 (4)	−0.0846 (4)	0.45076 (17)	0.0512 (7)
H13A	0.4434	−0.1362	0.4066	0.077*
H13B	0.3482	−0.1836	0.4856	0.077*
H13C	0.4728	−0.0019	0.4870	0.077*
C14	0.0646 (4)	−0.0948 (4)	0.34738 (17)	0.0433 (6)
H14A	0.1261	−0.1424	0.3028	0.065*
H14B	−0.0455	−0.0200	0.3212	0.065*
H14C	0.0221	−0.1970	0.3782	0.065*
C15	0.1100 (5)	0.1057 (4)	0.47614 (17)	0.0496 (7)
H15A	0.2007	0.1864	0.5130	0.074*
H15B	0.0697	0.0088	0.5106	0.074*
H15C	−0.0014	0.1765	0.4480	0.074*
C16	0.7654 (4)	0.3823 (5)	0.2870 (2)	0.0702 (10)
H16A	0.8933	0.4337	0.2919	0.105*
H16B	0.7736	0.2487	0.2898	0.105*
H16C	0.7099	0.4277	0.3338	0.105*
C17	0.1318 (3)	0.7016 (3)	0.09444 (12)	0.0283 (4)
O18	−0.0215 (2)	0.6227 (2)	0.08811 (11)	0.0374 (4)
C19	0.1360 (3)	0.9103 (3)	0.09008 (14)	0.0340 (5)
H19A	0.2374	0.9573	0.1369	0.041*
H19B	0.1669	0.9482	0.0353	0.041*
C20	−0.0465 (4)	0.9893 (3)	0.09718 (15)	0.0372 (5)
N21	−0.1875 (3)	1.0566 (3)	0.10290 (15)	0.0513 (6)

	U11	U22	U33	U12	U13	U23
C1	0.0333 (10)	0.0234 (10)	0.0361 (11)	0.0038 (9)	0.0125 (8)	−0.0038 (9)
C2	0.0278 (11)	0.0393 (14)	0.0574 (15)	0.0051 (10)	0.0160 (10)	−0.0009 (12)
C3	0.0269 (10)	0.0385 (14)	0.0575 (15)	−0.0046 (10)	0.0159 (10)	−0.0048 (11)
C4	0.0391 (11)	0.0325 (12)	0.0511 (14)	−0.0060 (10)	0.0187 (10)	0.0034 (11)
N5	0.0344 (9)	0.0239 (9)	0.0359 (10)	−0.0030 (8)	0.0091 (7)	0.0008 (8)
C6	0.0429 (12)	0.0234 (10)	0.0331 (11)	−0.0014 (9)	0.0090 (9)	−0.0037 (9)
N7	0.0327 (8)	0.0233 (9)	0.0310 (9)	0.0052 (8)	0.0099 (7)	−0.0018 (8)
C8	0.0558 (14)	0.0215 (11)	0.0508 (14)	0.0034 (10)	0.0282 (11)	−0.0025 (10)
C9	0.0314 (9)	0.0258 (10)	0.0289 (10)	0.0031 (9)	0.0038 (8)	−0.0018 (9)
O10	0.0546 (10)	0.0241 (8)	0.0414 (9)	0.0088 (8)	0.0147 (7)	−0.0021 (7)
O11	0.0570 (9)	0.0218 (7)	0.0366 (8)	0.0036 (8)	0.0187 (7)	0.0002 (7)
C12	0.0557 (13)	0.0239 (11)	0.0341 (12)	0.0063 (11)	0.0124 (10)	0.0032 (10)
C13	0.0667 (17)	0.0402 (13)	0.0417 (14)	0.0094 (13)	0.0000 (12)	0.0058 (12)
C14	0.0537 (14)	0.0294 (11)	0.0482 (14)	−0.0010 (11)	0.0138 (11)	−0.0000 (11)
C15	0.0788 (18)	0.0346 (12)	0.0431 (14)	0.0021 (13)	0.0300 (13)	0.0024 (11)
C16	0.0317 (12)	0.070 (2)	0.099 (3)	0.0032 (14)	−0.0084 (14)	0.015 (2)
C17	0.0360 (10)	0.0258 (10)	0.0230 (10)	−0.0026 (9)	0.0059 (8)	−0.0023 (8)
O18	0.0355 (8)	0.0322 (8)	0.0445 (9)	−0.0042 (7)	0.0085 (7)	−0.0065 (7)
C19	0.0398 (12)	0.0286 (11)	0.0321 (11)	−0.0018 (10)	0.0044 (9)	0.0035 (9)
C20	0.0506 (14)	0.0270 (11)	0.0325 (11)	0.0005 (11)	0.0058 (10)	−0.0004 (9)
N21	0.0589 (13)	0.0413 (13)	0.0545 (13)	0.0095 (12)	0.0139 (11)	−0.0015 (11)

C1—N7	1.472 (3)	C9—O11	1.357 (3)
C1—C6	1.533 (3)	O11—C12	1.465 (3)
C1—C2	1.544 (3)	C12—C14	1.512 (4)
C1—H1	1.0000	C12—C13	1.522 (3)
C2—C16	1.529 (4)	C12—C15	1.526 (3)
C2—C3	1.533 (4)	C13—H13A	0.9800
C2—H2	1.0000	C13—H13B	0.9800
C3—C4	1.516 (4)	C13—H13C	0.9800
C3—H3A	0.9900	C14—H14A	0.9800
C3—H3B	0.9900	C14—H14B	0.9800
C4—N5	1.470 (3)	C14—H14C	0.9800
C4—H4A	0.9900	C15—H15A	0.9800
C4—H4B	0.9900	C15—H15B	0.9800
N5—C17	1.345 (3)	C15—H15C	0.9800
N5—C6	1.467 (3)	C16—H16A	0.9800
C6—H6A	0.9900	C16—H16B	0.9800
C6—H6B	0.9900	C16—H16C	0.9800
N7—C9	1.349 (3)	C17—O18	1.228 (3)
N7—C8	1.451 (3)	C17—C19	1.530 (3)
C8—H8A	0.9800	C19—C20	1.459 (3)
C8—H8B	0.9800	C19—H19A	0.9900
C8—H8C	0.9800	C19—H19B	0.9900
C9—O10	1.223 (3)	C20—N21	1.147 (3)
N7—C1—C6	112.35 (17)	O10—C9—O11	123.9 (2)
N7—C1—C2	114.38 (18)	N7—C9—O11	110.90 (18)
C6—C1—C2	111.59 (19)	C9—O11—C12	121.04 (17)
N7—C1—H1	105.9	O11—C12—C14	110.10 (18)
C6—C1—H1	105.9	O11—C12—C13	110.3 (2)
C2—C1—H1	105.9	C14—C12—C13	112.8 (2)
C16—C2—C3	112.4 (2)	O11—C12—C15	101.76 (19)
C16—C2—C1	110.6 (2)	C14—C12—C15	110.7 (2)
C3—C2—C1	114.31 (19)	C13—C12—C15	110.8 (2)
C16—C2—H2	106.3	C12—C13—H13A	109.5
C3—C2—H2	106.3	C12—C13—H13B	109.5
C1—C2—H2	106.3	H13A—C13—H13B	109.5
C4—C3—C2	111.2 (2)	C12—C13—H13C	109.5
C4—C3—H3A	109.4	H13A—C13—H13C	109.5
C2—C3—H3A	109.4	H13B—C13—H13C	109.5
C4—C3—H3B	109.4	C12—C14—H14A	109.5
C2—C3—H3B	109.4	C12—C14—H14B	109.5
H3A—C3—H3B	108.0	H14A—C14—H14B	109.5
N5—C4—C3	110.11 (18)	C12—C14—H14C	109.5
N5—C4—H4A	109.6	H14A—C14—H14C	109.5
C3—C4—H4A	109.6	H14B—C14—H14C	109.5
N5—C4—H4B	109.6	C12—C15—H15A	109.5
C3—C4—H4B	109.6	C12—C15—H15B	109.5
H4A—C4—H4B	108.2	H15A—C15—H15B	109.5
C17—N5—C6	119.57 (19)	C12—C15—H15C	109.5
C17—N5—C4	126.53 (19)	H15A—C15—H15C	109.5
C6—N5—C4	113.55 (19)	H15B—C15—H15C	109.5
N5—C6—C1	112.52 (19)	C2—C16—H16A	109.5
N5—C6—H6A	109.1	C2—C16—H16B	109.5
C1—C6—H6A	109.1	H16A—C16—H16B	109.5
N5—C6—H6B	109.1	C2—C16—H16C	109.5
C1—C6—H6B	109.1	H16A—C16—H16C	109.5
H6A—C6—H6B	107.8	H16B—C16—H16C	109.5
C9—N7—C8	121.94 (17)	O18—C17—N5	123.7 (2)
C9—N7—C1	118.25 (17)	O18—C17—C19	119.5 (2)
C8—N7—C1	119.80 (18)	N5—C17—C19	116.7 (2)
N7—C8—H8A	109.5	C20—C19—C17	111.4 (2)
N7—C8—H8B	109.5	C20—C19—H19A	109.3
H8A—C8—H8B	109.5	C17—C19—H19A	109.3
N7—C8—H8C	109.5	C20—C19—H19B	109.3
H8A—C8—H8C	109.5	C17—C19—H19B	109.3
H8B—C8—H8C	109.5	H19A—C19—H19B	108.0
O10—C9—N7	125.24 (18)	N21—C20—C19	177.9 (3)
N7—C1—C2—C16	43.0 (3)	C2—C1—N7—C8	67.0 (3)
C6—C1—C2—C16	171.9 (2)	C8—N7—C9—O10	178.8 (2)
N7—C1—C2—C3	−85.0 (3)	C1—N7—C9—O10	0.2 (3)
C6—C1—C2—C3	43.9 (3)	C8—N7—C9—O11	−0.3 (3)
C16—C2—C3—C4	−175.6 (2)	C1—N7—C9—O11	−178.92 (17)
C1—C2—C3—C4	−48.5 (3)	O10—C9—O11—C12	−4.7 (3)
C2—C3—C4—N5	55.2 (3)	N7—C9—O11—C12	174.44 (18)
C3—C4—N5—C17	126.0 (2)	C9—O11—C12—C14	−60.1 (3)
C3—C4—N5—C6	−60.9 (3)	C9—O11—C12—C13	65.0 (3)
C17—N5—C6—C1	−129.3 (2)	C9—O11—C12—C15	−177.46 (19)
C4—N5—C6—C1	57.1 (3)	C6—N5—C17—O18	3.4 (3)
N7—C1—C6—N5	83.0 (2)	C4—N5—C17—O18	176.1 (2)
C2—C1—C6—N5	−47.0 (3)	C6—N5—C17—C19	−177.8 (2)
C6—C1—N7—C9	117.2 (2)	C4—N5—C17—C19	−5.1 (3)
C2—C1—N7—C9	−114.3 (2)	O18—C17—C19—C20	12.5 (3)
C6—C1—N7—C8	−61.5 (3)	N5—C17—C19—C20	−166.36 (18)