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

HRID 1184825Notes

Reaction equation

HRID 1184825 reaction equation
Br[C:2]1[C:3]([C:9]#[N:10])=[N:4][C:5]([Br:8])=[CH:6][N:7]=1.[C:11]([C:13]([C:16]1[CH:17]=[C:18]([CH:34]=[CH:35][CH:36]=1)[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[C:24]([NH:29][C:30](=[O:33])[CH2:31][SH:32])[CH:23]=1)=[O:20])([CH3:15])[CH3:14])#[N:12].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[NH2:10][C:9]1[C:3]2[C:2](=[N:7][CH:6]=[C:5]([Br:8])[N:4]=2)[S:32][C:31]=1[C:30]([NH:29][C:24]1[CH:23]=[C:22]([NH:21][C:19](=[O:20])[C:18]2[CH:34]=[CH:35][CH:36]=[C:16]([C:13]([C:11]#[N:12])([CH3:14])[CH3:15])[CH:17]=2)[CH:27]=[CH:26][C:25]=1[CH3:28])=[O:33]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 707010703,6-Dibromopyrazine-2-carbonitrileHCID 866801643-(2-cyanopropan-2-yl)-N-(3-(2-mercaptoacetamido)-4-methylphenyl)benzamide

Product 1

HCID 547563117-amino-2-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 77.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3,6-dibromopyrazine-2-carbonitrile 15 (286 mg, 1.089 mmol) and 3-(2-cyanopropan-2-yl)-N-(3-(2-mercaptoacetamido)-4-methylphenyl)benzamide 16 (400 mg, 1.089 mmol) in ethanol (5 mL) was added potassium carbonate (211 mg, 1.524 mmol). The reaction was stirred 1 h at rt and 2 h at 50° C. Quenched in cooled 1N HCl solution (aq), the resulting precipitate was collected and dried to give crude compound 17 (588 mg). Purification by chromatography (0-10% EtOAc in CH2Cl2) gave pure 7-amino-2-bromo-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 17 (463 mg, 77%). 1H-NMR (400 MHz, DMSO-d6) 1.75 (s, 6H), 2.21 (s, 3H), 7.09 (br s, 2H), 7.27 (d, J=8.6 Hz, 1H), 7.60 (t, J=7.8 Hz, 2H), 7.75 (d, J=7.8 Hz, 1H), 7.81 (br s, 1H), 7.95 (d, J=7.0, 1H), 8.05 (s, 1H), 8.93 (br s, 1H), 9.58 (br s, 1H), 10.32 (br s, 1H). (m/z)=549 and 551 (M+H)+.

Workup

  1. customQuenched in cooled 1N HCl solution (aq)
  2. customthe resulting precipitate was collected
  3. customdried
  4. customto give crude compound 17 (588 mg)
  5. customPurification by chromatography (0-10% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-fdc1339da0b948ceb36fdf2c39d69666
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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