Pyrrolidine → 2-(7-pyrrolidin-1-yl-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898659Notes

Reaction equation

HRID 1898659 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[S:32][C:31]5[C:26](=[N:27][CH:28]=[CH:29][C:30]=5Cl)[CH:25]=4)[N:22]=3)[N:17]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].[NH:43]1[CH2:47][CH2:46][CH2:45][CH2:44]1>>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[S:32][C:31]5[C:26](=[N:27][CH:28]=[CH:29][C:30]=5[N:43]5[CH2:47][CH2:46][CH2:45][CH2:44]5)[CH:25]=4)[N:22]=3)[N:17]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2]

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 584385872-(7-chloro-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Product 1

HCID 673862912-(7-pyrrolidin-1-yl-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amideYield 85.6%

Procedure

A solution of 2-(7-chloro-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (40 mg, 0.064 mmol) in pyrrolidine (5.32 ml, 64.3 mmol) was heated in a microwave reactor at 100° C. for 2 h. The reaction mixture was evaporated to dryness under vacuum. The crude residue was suspended in MeOH (0.5 mL) and the resultant solid collected by filtration, washing with MeOH, to give 36 mg (85%) 2-(7-pyrrolidin-1-yl-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.

Workup

  1. customThe reaction mixture was evaporated to dryness under vacuum
  2. filtrationthe resultant solid collected by filtration
  3. washwashing with MeOH

Sources & evidence

ORD record
ord-647b3a3fc72742e58a9bffd995633b38
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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