Methanol → (R)-cyclopropyl-{[2-(7-methoxy-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-acetic acid

HRID 1898662Notes

Reaction equation

[CH3:1][O-:2].[Na+].C[OH:5].C(C1CN([C:12](=[O:47])[C@H:13]([NH:17][C:18]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[C:26]([C:29]4[S:37][C:36]5[C:31](=[N:32][CH:33]=[CH:34][C:35]=5Cl)[CH:30]=4)[N:27]=3)[N:22]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[CH:21]=2)=[O:19])[CH:14]2[CH2:16][CH2:15]2)C1)#N>>[CH:14]1([C@@H:13]([NH:17][C:18]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[C:26]([C:29]4[S:37][C:36]5[C:31](=[N:32][CH:33]=[CH:34][C:35]=5[O:2][CH3:1])[CH:30]=4)[N:27]=3)[N:22]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:44])[CH3:45])[CH:21]=2)=[O:19])[C:12]([OH:5])=[O:47])[CH2:15][CH2:16]1

Participants

Reactant 3

HCID 887Methanol

HCID 10942334Sodium Methoxide

HCID 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 67386740(R)-cyclopropyl-{[2-(7-methoxy-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-acetic acidYield 57%

Conditions

Temperature: 100 °C

Procedure

To a solution of sodium methoxide in MeOH (0.5 M, 0.97 mL, 0.49 mmol) was added 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 (35 mg, 0.056 mmol) and reaction mixture was stirred at 100° C. for 1 h under microwave assisted conditions. The reaction mixture was evaporated to dryness and the crude residue was purified by preparative TLC (CH2Cl2:MeOH:NH4OH, 80:19:1) to give 18 mg (57%) of (R)-cyclopropyl-{[2-(7-methoxy-thieno[3,2-b]pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-acetic acid. MS: (M+H)+=554; (M−H])−=552.

Workup

customThe reaction mixture was evaporated to dryness
customthe crude residue was purified by preparative TLC (CH2Cl2:MeOH:NH4OH, 80:19:1)

Sources & evidence

ORD record: ord-593578425ed44294b6600734e0b02932
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518945B2

Reaction notes

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