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

HRID 1184902Notes

Reaction equation

HRID 1184902 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:22])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([C:20]#[N:21])([CH3:19])[CH3:18])[CH:12]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].C(N(CC)CC)C.[Cl:30][C:31]1[N:36]=[C:35]2[S:37][C:38]([C:40](Cl)=[O:41])=[CH:39][C:34]2=[N:33][CH:32]=1>C(Cl)Cl>[Cl:30][C:31]1[N:36]=[C:35]2[S:37][C:38]([C:40]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][C:10](=[O:22])[C:11]4[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([C:20]#[N:21])([CH3:19])[CH3:18])[CH:12]=4)[CH:5]=[CH:6][C:7]=3[CH3:8])=[O:41])=[CH:39][C:34]2=[N:33][CH:32]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 67125542N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamideHCID 866801793-Chlorothieno[2,3-b]pyrazine-6-carbonyl chloride

Product 1

HCID 866801803-chloro-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide 5 (2.56 mmol, 750 mg) and triethylamine (12.78 mmol, 1.782 mL) in CH2Cl21 ml at 0° C. was added 3-chlorothieno[2,3-b]pyrazine-6-carbonyl chloride 94 in 1 mL CH2Cl2 and stirred at rt for 1 h. The reaction mixture was quenched with water, extracted with CH2Cl2 (2×). The organic layer was dried and concentrated under reduced pressure. Purified with column chromatography (10-20% ethyl acetate in CH2Cl2) gave 3-chloro-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 95 (1.04 g, 83%). NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 2.26 (s, 3H), 7.32 (d, J=8.2 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.64 (dd, J=8.2 Hz and 2.0 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.87 (d, J=2.3 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.05 (s, 1H), 8.57 (s, 1H), 8.98 (s, 1H), 10.37 (s, 1H), 10.56 (s, 1H). (m/z)=490 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with CH2Cl2 (2×)
  3. customThe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customPurified with column chromatography (10-20% ethyl acetate in CH2Cl2)

Sources & evidence

ORD record
ord-ebf02fe74f604914a3de31ae6c9a132f
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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