(S)-Benzyl 2-[N-(5-chloro­pyridin-2-yl)­carbamo­yl]­pyrrolidine-1-carboxyl­ate

In the title compound, C₁₈H₁₈ClN₃O₃, the pyrrolidine ring adopts an envelope conformation. The dihedral angle between the phenyl ring and the pyridine ring is 28.30 (7)°. The crystal packing is stabilized by N—H...O and C—H...O hydrogen bonding.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.032
• wR factor = 0.087
• Data-to-parameter ratio = 17.7

checkCIF/PLATON results

No syntax errors found



Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.54
           From the CIF: _reflns_number_total               3991
           Count of symmetry unique reflns         2305
           Completeness (_total/calc)            173.15%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured      1686
           Fraction of Friedel pairs measured     0.731
           Are heavy atom types Z>Si present        yes
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C12    = .          S

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   0 ALERT level C = Check and explain
   4 ALERT level G = General alerts; check

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. Comment

The title compound is an important inhibitor of peptidyl deformylase (Patel et al., 2002). Its crystal structure is presented here.

The molecular structure is shown in Fig. 1. Bond lengths and angles are normal. The dihedral angle between the C6-benzene and O1/O2/N1/C8 planes is 50.56 (7)° and that between N3-pyridine and O3/N2/C12/C13 planes is 11.34 (11)°. The crystal packing is stabilized by N—H···O and C—H···O hydrogen bonding (Table 1).

Related literature

For general background, see: Patel et al. (1994 or??2002). For related structures, see He (2006); Kang et al. (2007).

S2. Experimental

N-Carbobenzyloxy-L-proline (1.0 g, 4 mmol) and triethylamine (0.4 g, 4 mmol) were dissolved in THF (15 ml). To the solution was added dropwise ethylchloroformate (0.44 g, 4 mmol) at 273 K. After the solution was stirred for 30 min, 5-chloropyridin-2-amine (4 mmol) was added over a period of 10 min. The resulting solution was stirred at 273 K for 1 h and then stirred at room temperature for a further 12 h, and finaly refluxed for 3 h. After cooling down to room temperature, the solution was diluted with ethyl acetate. After filtration and removal of solvent under reduced pressure, the residue was purified through column chromatography on silica gel to give the title compound. Colourless single crystals were obtained by recrystallization from an ethanol solution.

S3. Refinement

H atoms were placed at calculated positions with C–H = 0.93 or 0.97 Å and N—H = 0.86 Å, and refined using a riding model with U_iso(H) = 1.2U_eq(C,N).

Computing details

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2002); software used to prepare material for publication: SHELXTL (Bruker, 2002).

Figures

Fig. 1. The molecular structure of (I) with 30% probability displacement ellipsoids (arbitrary spheres for H atoms).

(I)

Crystal data

C18H18ClN3O3	F(000) = 752
Mr = 359.80	Dx = 1.380 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 8860 reflections
a = 6.2419 (14) Å	θ = 1.7–27.5°
b = 15.785 (4) Å	µ = 0.24 mm^−1
c = 17.574 (4) Å	T = 293 K
V = 1731.5 (7) Å^3	Block, colourless
Z = 4	0.39 × 0.32 × 0.21 mm

Data collection

Bruker APEXII area-detector diffractometer	3602 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.021
Graphite monochromator	θmax = 27.5°, θmin = 1.7°
ω scans	h = −8→8
22340 measured reflections	k = −20→20
3991 independent reflections	l = −22→22

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.032	H-atom parameters constrained
wR(F^2) = 0.088	w = 1/[σ^2(Fo^2) + (0.0474P)^2 + 0.1826P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
3991 reflections	Δρmax = 0.31 e Å^−3
226 parameters	Δρmin = −0.17 e Å^−3
0 restraints	Absolute structure: Flack (1983), Friedel pairs 1686
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.02 (6)

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.95345 (10)	−0.20996 (3)	0.56412 (3)	0.07666 (17)
O1	−0.26937 (16)	0.14607 (7)	0.81673 (7)	0.0519 (3)
O2	0.06298 (16)	0.14500 (7)	0.76457 (6)	0.0501 (3)
O3	0.1628 (2)	−0.07143 (9)	0.80223 (8)	0.0693 (4)
N1	0.0084 (2)	0.07818 (8)	0.87283 (7)	0.0475 (3)
N2	0.4701 (2)	−0.00045 (8)	0.77641 (7)	0.0454 (3)
H2B	0.5368	0.0460	0.7861	0.054*
N3	0.7472 (2)	−0.02296 (8)	0.69420 (8)	0.0536 (3)
C1	0.1709 (3)	0.21399 (11)	0.65153 (8)	0.0496 (3)
C2	0.3125 (3)	0.15325 (12)	0.62553 (10)	0.0624 (4)
H2A	0.2895	0.0966	0.6374	0.075*
C3	0.4874 (3)	0.17575 (12)	0.58222 (10)	0.0653 (5)
H3A	0.5817	0.1342	0.5653	0.078*
C4	0.5231 (3)	0.25886 (13)	0.56400 (10)	0.0640 (5)
H4A	0.6412	0.2741	0.5348	0.077*
C5	0.3837 (3)	0.31895 (12)	0.58906 (12)	0.0688 (5)
H5A	0.4071	0.3755	0.5766	0.083*
C6	0.2077 (3)	0.29728 (11)	0.63282 (10)	0.0581 (4)
H6A	0.1142	0.3392	0.6496	0.070*
C7	−0.0186 (3)	0.19016 (14)	0.69944 (11)	0.0647 (5)
H7A	−0.0953	0.2405	0.7156	0.078*
H7B	−0.1160	0.1545	0.6707	0.078*
C8	−0.0816 (2)	0.12430 (9)	0.81787 (9)	0.0435 (3)
C9	−0.1015 (3)	0.05911 (12)	0.94413 (10)	0.0595 (4)
H9A	−0.1788	0.0059	0.9409	0.071*
H9B	−0.2007	0.1039	0.9578	0.071*
C10	0.0824 (3)	0.05351 (14)	1.00050 (11)	0.0692 (5)
H10A	0.1218	0.1092	1.0192	0.083*
H10B	0.0453	0.0177	1.0434	0.083*
C11	0.2603 (3)	0.01519 (13)	0.95454 (10)	0.0615 (4)
H11A	0.2470	−0.0460	0.9528	0.074*
H11B	0.3988	0.0297	0.9760	0.074*
C12	0.2343 (2)	0.05386 (10)	0.87433 (9)	0.0452 (3)
H12A	0.3268	0.1036	0.8682	0.054*
C13	0.2818 (2)	−0.01228 (9)	0.81333 (9)	0.0443 (3)
C14	0.5688 (2)	−0.05511 (9)	0.72421 (8)	0.0429 (3)
C15	0.4942 (3)	−0.13553 (10)	0.70621 (10)	0.0559 (4)
H15A	0.3676	−0.1560	0.7272	0.067*
C16	0.6120 (3)	−0.18417 (10)	0.65659 (10)	0.0591 (4)
H16A	0.5669	−0.2384	0.6434	0.071*
C17	0.7966 (3)	−0.15139 (10)	0.62707 (9)	0.0526 (4)
C18	0.8584 (3)	−0.07138 (12)	0.64670 (10)	0.0577 (4)
H18A	0.9840	−0.0498	0.6259	0.069*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0931 (4)	0.0654 (3)	0.0714 (3)	0.0266 (3)	0.0201 (3)	−0.0079 (2)
O1	0.0333 (5)	0.0546 (6)	0.0679 (7)	0.0003 (5)	0.0041 (5)	−0.0087 (5)
O2	0.0356 (5)	0.0637 (6)	0.0511 (6)	0.0016 (5)	0.0046 (4)	0.0090 (5)
O3	0.0523 (6)	0.0655 (7)	0.0901 (9)	−0.0205 (6)	0.0217 (7)	−0.0175 (7)
N1	0.0359 (6)	0.0534 (7)	0.0533 (7)	0.0013 (5)	0.0124 (5)	0.0040 (6)
N2	0.0392 (6)	0.0433 (6)	0.0536 (7)	−0.0051 (5)	0.0092 (5)	−0.0038 (5)
N3	0.0452 (7)	0.0544 (8)	0.0611 (8)	−0.0054 (6)	0.0140 (6)	−0.0098 (6)
C1	0.0451 (8)	0.0596 (9)	0.0440 (7)	0.0048 (7)	−0.0019 (6)	0.0045 (7)
C2	0.0672 (11)	0.0545 (9)	0.0655 (10)	0.0071 (8)	0.0099 (9)	0.0058 (8)
C3	0.0619 (11)	0.0719 (11)	0.0621 (10)	0.0156 (9)	0.0104 (9)	−0.0038 (9)
C4	0.0516 (10)	0.0830 (13)	0.0573 (10)	−0.0071 (9)	0.0055 (8)	0.0029 (9)
C5	0.0689 (12)	0.0586 (10)	0.0789 (12)	−0.0106 (9)	0.0054 (10)	0.0026 (9)
C6	0.0559 (10)	0.0561 (9)	0.0622 (9)	0.0067 (8)	0.0023 (8)	−0.0062 (8)
C7	0.0445 (8)	0.0875 (13)	0.0620 (10)	0.0099 (9)	0.0012 (8)	0.0202 (9)
C8	0.0350 (7)	0.0429 (7)	0.0527 (8)	−0.0051 (6)	0.0051 (6)	−0.0083 (6)
C9	0.0516 (9)	0.0617 (10)	0.0651 (10)	0.0003 (8)	0.0228 (8)	0.0061 (8)
C10	0.0761 (13)	0.0759 (12)	0.0555 (10)	0.0100 (10)	0.0166 (9)	0.0082 (9)
C11	0.0577 (10)	0.0761 (12)	0.0506 (9)	0.0106 (9)	0.0049 (8)	0.0018 (8)
C12	0.0351 (7)	0.0506 (8)	0.0498 (8)	0.0005 (6)	0.0073 (6)	0.0003 (6)
C13	0.0368 (7)	0.0462 (8)	0.0498 (8)	−0.0028 (6)	0.0057 (6)	0.0034 (6)
C14	0.0403 (7)	0.0455 (7)	0.0429 (7)	0.0008 (6)	0.0037 (6)	0.0011 (6)
C15	0.0595 (10)	0.0471 (8)	0.0611 (9)	−0.0075 (7)	0.0118 (8)	−0.0007 (7)
C16	0.0752 (12)	0.0412 (7)	0.0610 (10)	0.0023 (8)	0.0059 (9)	−0.0033 (7)
C17	0.0603 (10)	0.0505 (8)	0.0470 (8)	0.0160 (7)	0.0028 (7)	−0.0004 (7)
C18	0.0500 (9)	0.0618 (10)	0.0611 (10)	−0.0013 (8)	0.0144 (8)	−0.0059 (8)

Geometric parameters (Å, º)

Cl1—C17	1.7429 (16)	C5—H5A	0.9300
O1—C8	1.2215 (18)	C6—H6A	0.9300
O2—C8	1.3411 (18)	C7—H7A	0.9700
O2—C7	1.441 (2)	C7—H7B	0.9700
O3—C13	1.2091 (18)	C9—C10	1.519 (3)
N1—C8	1.334 (2)	C9—H9A	0.9700
N1—C9	1.4601 (19)	C9—H9B	0.9700
N1—C12	1.462 (2)	C10—C11	1.501 (3)
N2—C13	1.3552 (18)	C10—H10A	0.9700
N2—C14	1.4018 (18)	C10—H10B	0.9700
N2—H2B	0.8600	C11—C12	1.545 (2)
N3—C18	1.328 (2)	C11—H11A	0.9700
N3—C14	1.3326 (19)	C11—H11B	0.9700
C1—C6	1.374 (2)	C12—C13	1.526 (2)
C1—C2	1.382 (2)	C12—H12A	0.9800
C1—C7	1.500 (2)	C14—C15	1.389 (2)
C2—C3	1.377 (3)	C15—C16	1.375 (2)
C2—H2A	0.9300	C15—H15A	0.9300
C3—C4	1.369 (3)	C16—C17	1.365 (3)
C3—H3A	0.9300	C16—H16A	0.9300
C4—C5	1.360 (3)	C17—C18	1.365 (3)
C4—H4A	0.9300	C18—H18A	0.9300
C5—C6	1.384 (3)
C8—O2—C7	115.93 (12)	C10—C9—H9B	111.3
C8—N1—C9	122.41 (13)	H9A—C9—H9B	109.2
C8—N1—C12	124.27 (12)	C11—C10—C9	103.41 (14)
C9—N1—C12	112.57 (13)	C11—C10—H10A	111.1
C13—N2—C14	127.55 (13)	C9—C10—H10A	111.1
C13—N2—H2B	116.2	C11—C10—H10B	111.1
C14—N2—H2B	116.2	C9—C10—H10B	111.1
C18—N3—C14	117.81 (14)	H10A—C10—H10B	109.0
C6—C1—C2	118.54 (16)	C10—C11—C12	104.72 (14)
C6—C1—C7	120.39 (16)	C10—C11—H11A	110.8
C2—C1—C7	121.07 (16)	C12—C11—H11A	110.8
C3—C2—C1	120.71 (17)	C10—C11—H11B	110.8
C3—C2—H2A	119.6	C12—C11—H11B	110.8
C1—C2—H2A	119.6	H11A—C11—H11B	108.9
C4—C3—C2	120.37 (17)	N1—C12—C13	110.77 (13)
C4—C3—H3A	119.8	N1—C12—C11	102.82 (12)
C2—C3—H3A	119.8	C13—C12—C11	110.52 (13)
C5—C4—C3	119.24 (18)	N1—C12—H12A	110.8
C5—C4—H4A	120.4	C13—C12—H12A	110.8
C3—C4—H4A	120.4	C11—C12—H12A	110.8
C4—C5—C6	121.01 (18)	O3—C13—N2	124.20 (14)
C4—C5—H5A	119.5	O3—C13—C12	121.48 (13)
C6—C5—H5A	119.5	N2—C13—C12	114.25 (13)
C1—C6—C5	120.13 (16)	N3—C14—C15	122.55 (14)
C1—C6—H6A	119.9	N3—C14—N2	113.06 (13)
C5—C6—H6A	119.9	C15—C14—N2	124.37 (14)
O2—C7—C1	106.91 (13)	C16—C15—C14	118.41 (16)
O2—C7—H7A	110.3	C16—C15—H15A	120.8
C1—C7—H7A	110.3	C14—C15—H15A	120.8
O2—C7—H7B	110.3	C17—C16—C15	118.72 (16)
C1—C7—H7B	110.3	C17—C16—H16A	120.6
H7A—C7—H7B	108.6	C15—C16—H16A	120.6
O1—C8—N1	124.73 (14)	C18—C17—C16	119.56 (15)
O1—C8—O2	124.45 (15)	C18—C17—Cl1	119.50 (14)
N1—C8—O2	110.81 (12)	C16—C17—Cl1	120.94 (13)
N1—C9—C10	102.49 (14)	N3—C18—C17	122.93 (16)
N1—C9—H9A	111.3	N3—C18—H18A	118.5
C10—C9—H9A	111.3	C17—C18—H18A	118.5
N1—C9—H9B	111.3
C6—C1—C2—C3	0.4 (3)	C8—N1—C12—C11	171.05 (14)
C7—C1—C2—C3	−179.33 (16)	C9—N1—C12—C11	0.82 (18)
C1—C2—C3—C4	−0.3 (3)	C10—C11—C12—N1	−23.25 (18)
C2—C3—C4—C5	−0.1 (3)	C10—C11—C12—C13	−141.51 (15)
C3—C4—C5—C6	0.3 (3)	C14—N2—C13—O3	−5.0 (3)
C2—C1—C6—C5	−0.2 (3)	C14—N2—C13—C12	172.18 (13)
C7—C1—C6—C5	179.54 (17)	N1—C12—C13—O3	−43.5 (2)
C4—C5—C6—C1	−0.2 (3)	C11—C12—C13—O3	69.8 (2)
C8—O2—C7—C1	174.62 (14)	N1—C12—C13—N2	139.26 (13)
C6—C1—C7—O2	−123.60 (17)	C11—C12—C13—N2	−107.46 (15)
C2—C1—C7—O2	56.1 (2)	C18—N3—C14—C15	−1.6 (2)
C9—N1—C8—O1	−9.5 (2)	C18—N3—C14—N2	176.92 (15)
C12—N1—C8—O1	−178.78 (15)	C13—N2—C14—N3	176.11 (14)
C9—N1—C8—O2	169.35 (14)	C13—N2—C14—C15	−5.5 (2)
C12—N1—C8—O2	0.0 (2)	N3—C14—C15—C16	1.3 (3)
C7—O2—C8—O1	−5.2 (2)	N2—C14—C15—C16	−177.01 (15)
C7—O2—C8—N1	175.97 (14)	C14—C15—C16—C17	−0.1 (3)
C8—N1—C9—C10	−149.02 (15)	C15—C16—C17—C18	−0.7 (3)
C12—N1—C9—C10	21.42 (19)	C15—C16—C17—Cl1	179.81 (14)
N1—C9—C10—C11	−35.11 (19)	C14—N3—C18—C17	0.7 (3)
C9—C10—C11—C12	36.48 (19)	C16—C17—C18—N3	0.4 (3)
C8—N1—C12—C13	−70.87 (18)	Cl1—C17—C18—N3	179.94 (14)
C9—N1—C12—C13	118.90 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2B···O1^i	0.86	2.06	2.9148 (17)	172
C6—H6A···O3^ii	0.93	2.39	3.308 (2)	171

Symmetry codes: (i) x+1, y, z; (ii) −x, y+1/2, −z+3/2.