7-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide → 7-cyano-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184854Notes

Reaction equation

HRID 1184854 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][N:9]=2)[S:4][C:3]=1[C:11]([NH:13][C:14]1[CH:19]=[C:18]([NH:20][C:21](=[O:33])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([C:31]#[N:32])([CH3:30])[CH3:29])[CH:23]=2)[CH:17]=[CH:16][C:15]=1[CH3:34])=[O:12].[Cu][C:36]#[N:37]>CN1C(=O)CCC1.[NH4+].[OH-].[Cu]I>[C:36]([C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][N:9]=2)[S:4][C:3]=1[C:11]([NH:13][C:14]1[CH:19]=[C:18]([NH:20][C:21](=[O:33])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([C:31]#[N:32])([CH3:30])[CH3:29])[CH:23]=2)[CH:17]=[CH:16][C:15]=1[CH3:34])=[O:12])#[N:37]

Participants

6

Reactant 2

HCID 671255437-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamideHCID 178418546HCID 178418546, compound

Product 1

HCID 671256307-cyano-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 39.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13387N-methyl-2-pyrrolidoneSolventHCID 14923Ammonium HydroxideSolvent

Procedure

A solution of 7-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 42 (20 mg, 0.037 mmol), copper(i) cyanide (3.35 mg, 0.037 mmol) and copper(i) iodide (7.13 mg, 0.037 mmol) in NMP (1 mL) was stirred 10 min at 150° C. in microwave with cooling. Poured in NH4OH solution and extracted with EtOAc. Organic layer was washed with brine, dried and evaporated. Purification by chromatography (20% EtOAc in CH2Cl2) gave the title compound 7-cyano-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 43b (7 mg, 38.9%). NMR (400 MHz, DMSO-d6) 2.31 (s, 3H), 7.33 (d, J=8.2 Hz, 1H), 7.58-7.69 (m, 2H), 7.76 (d, J=7.8 Hz, 1H), 7.94-8.00 (m, 2H), 8.06 (m, 1H), 8.95 (d, J=2.3 Hz, !H), 9.06 (d, J=2.3 Hz, 1H), 10.41 (s, 1H), 10.77 (s, 1H). (m/z)=481 (M+H)+.

Workup

  1. temperaturewith cooling
  2. extractionextracted with EtOAc
  3. washOrganic layer was washed with brine
  4. customdried
  5. customevaporated
  6. customPurification by chromatography (20% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-1ce3882b30614253994edcad70ed5fc0
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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