3-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1-ethyl-2-oxo-pyrrolidin-3-yl)oxy-N-(5-methylpyrazin-2-yl)benzamide → 3-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3S)-1-ethyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide

HRID 600522Notes

Reaction equation

HRID 600522 reaction equation
[N:1]1([C:5]([C:7]2[N:12]=[CH:11][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:27]=[C:28]([O:30][CH:31]4[CH2:35][CH2:34][N:33]([CH2:36][CH3:37])[C:32]4=[O:38])[CH:29]=3)[C:17]([NH:19][C:20]3[CH:25]=[N:24][C:23]([CH3:26])=[CH:22][N:21]=3)=[O:18])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.N1(C(C2N=CC(OC3C=C(C=C(O[C@@H]4CCN(CC)C4=O)C=3)C(NC3C=NC(C)=CN=3)=O)=CC=2)=O)CCC1>>[N:1]1([C:5]([C:7]2[N:12]=[CH:11][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:27]=[C:28]([O:30][C@H:31]4[CH2:35][CH2:34][N:33]([CH2:36][CH3:37])[C:32]4=[O:38])[CH:29]=3)[C:17]([NH:19][C:20]3[CH:25]=[N:24][C:23]([CH3:26])=[CH:22][N:21]=3)=[O:18])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 249526633-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1-ethyl-2-oxo-pyrrolidin-3-yl)oxy-N-(5-methylpyrazin-2-yl)benzamideHCID 249533703-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3R)-1-ethyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide

Product 1

HCID 249533713-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3S)-1-ethyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamideYield 26%

Procedure

From racemic 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1-ethyl-2-oxo-pyrrolidin-3-yl)oxy-N-(5-methylpyrazin-2-yl)benzamide (197 mg, 0.38 mmol) (Example 10), 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(3R)-1-ethyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide was separated from its enantiomer by chiral HPLC using a Merck 50 mm 20 μm Chiralcel OJ column eluting with methanol at a flow rate of 60 mL/min. 197 mg of racemic material was separated in 1 injection of 5 mL at 40 mg/ml in methanol to afford the product which eluted after its enantiomer to afford the product (51 mg, 26%). 1H NMR δ (300 MHz, CDCl3) 1.18 (t, 3H), 2.13-2.26 (m, 1H), 2.36 (quintet, 2H), 2.52-2.69 (m, 4H), 3.36-3.58 (m, 4H), 4.25 (t, 2H), 4.71 (t, 2H), 4.95 (t, 1H), 6.98 (s, 1H), 7.22 (s, 1H), 7.39 (d, 1H), 7.47 (s, 1H), 8.12 (d, 1H), 8.14 (s, 1H), 8.33 (s, 1H), 8.56 (s, 1H), 9.53 (s, 1H); m/z 517 (M+H)+.

Workup

  1. washeluting with methanol at a flow rate of 60 mL/min
  2. custom197 mg of racemic material was separated in 1 injection of 5 mL at 40 mg/ml in methanol
  3. customto afford the product which
  4. washeluted after its enantiomer

Sources & evidence

ORD record
ord-91b5dcd07c2d4e3099c036e677589faf
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

Loading…