2,2,2-Trifluoroethanol → 2-[7-(2,2,2-trifluoroethoxy)-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 1898660Notes

Reaction equation

HRID 1898660 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].[C:9]([CH:11]1[CH2:14][N:13]([C:15](=[O:50])[C@H:16]([NH:20][C:21]([C:23]2[C:31]3[C:26](=[N:27][CH:28]=[C:29]([C:32]4[S:40][C:39]5[C:34](=[N:35][CH:36]=[CH:37][C:38]=5Cl)[CH:33]=4)[N:30]=3)[N:25]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[CH:24]=2)=[O:22])[CH:17]2[CH2:19][CH2:18]2)[CH2:12]1)#[N:10].CCOC(C)=O>CN(C=O)C>[C:9]([CH:11]1[CH2:12][N:13]([C:15](=[O:50])[C@H:16]([NH:20][C:21]([C:23]2[C:31]3[C:26](=[N:27][CH:28]=[C:29]([C:32]4[S:40][C:39]5[C:34](=[N:35][CH:36]=[CH:37][C:38]=5[O:6][CH2:5][C:4]([F:8])([F:7])[F:3])[CH:33]=4)[N:30]=3)[N:25]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:48])([CH3:47])[CH3:49])[CH:24]=2)=[O:22])[CH:17]2[CH2:19][CH2:18]2)[CH2:14]1)#[N:10]

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 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 673867832-[7-(2,2,2-trifluoroethoxy)-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 85.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of sodium hydride (60% dispersion, 9.6 mg, 0.24 mmol) in DMF (3 mL) was added 2,2,2-trifluoroethanol (59 μL, 0.80 mmol) and then 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 (50 mg, 0.08 mmol). The reaction mixture was stirred at 100° C. for 1 h under microwave assisted conditions then poured into EtOAc (20 mL) and washed with water (5×20 mL). The organic phase was evaporated under vacuum and the crude residue was purified by preparative TLC (CH2Cl2:MeOH:NH4OH, 94:5.7:0.3) to give 47 mg (85%) of 2-[7-(2,2,2-trifluoroethoxy)-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. washwashed with water (5×20 mL)
  2. customThe organic phase was evaporated under vacuum
  3. customthe crude residue was purified by preparative TLC (CH2Cl2:MeOH:NH4OH, 94:5.7:0.3)

Sources & evidence

ORD record
ord-edfda888b72d4624bd1b5ecd0e50d062
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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