Methyl 3-(3-thienyl)benzoate → N-(2-methyl-5-(3-(thiophen-3-yl)benzamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184891Notes

Reaction equation

HRID 1184891 reaction equation
Cl.[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:21])=[C:7]([NH:9][C:10]([C:12]2[S:20][C:15]3=[N:16][CH:17]=[CH:18][N:19]=[C:14]3[CH:13]=2)=[O:11])[CH:8]=1.C[Al](C)C.[S:26]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]=[C:33]([CH:38]=[CH:39][CH:40]=2)[C:34](OC)=[O:35])=[CH:27]1>C1(C)C=CC=CC=1>[CH3:21][C:6]1[CH:5]=[CH:4][C:3]([NH:2][C:34](=[O:35])[C:33]2[CH:38]=[CH:39][CH:40]=[C:31]([C:28]3[CH:29]=[CH:30][S:26][CH:27]=3)[CH:32]=2)=[CH:8][C:7]=1[NH:9][C:10]([C:12]1[S:20][C:15]2=[N:16][CH:17]=[CH:18][N:19]=[C:14]2[CH:13]=1)=[O:11]

Participants

5

Reactant 3

HCID 3564198Methyl 3-(3-thienyl)benzoateHCID 16682925TrimethylaluminumHCID 67125547N-(5-amino-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide hydrochloride

Product 1

HCID 54754767N-(2-methyl-5-(3-(thiophen-3-yl)benzamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 5.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of N-(5-amino-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide hydrochloride 29 (73.5 mg, 0.229 mmol) in toluene (1.5 mL) was added trimethylaluminum (0.458 mL, 0.916 mmol) and was stirred for 15 min. methyl 3-(thiophen-3-yl)benzoate 82 (50 mg, 0.229 mmol) in toluene (1.5 mL) was added. The reaction mixture was stirred overnight at 60° C. Quenched with a saturated solution of NaHCO3 and extracted twice with EtOAc. Organic layer was washed with brine, dried, and evaporated. Purification by HPLC gave the title compound N-(2-methyl-5-(3-(thiophen-3-yl)benzamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamide 83 (6 mg, 5%). NMR (400 MHz, DMSO-d6) 2.27 (s, 3H), 7.32 (d, J=8.2 Hz, 1H), 7.58 (t, J=7.8 Hz, 1H), 7.64-7.72 (m, 3H), 7.87 (d, J=7.8 Hz, 1H), 7.91 (d, J=2.3 Hz, 1H), 7.94 (d, J=7.8 Hz, 1H), 8.01 (dd, 2.7 Hz and 1.6 Hz, 1H), 8.27 (t, J=1.6 Hz, 1H), 8.55 (s, 1H), 8.76 (d, J=2.3 Hz, 1H), 8.89 (d, J=2.3 Hz, 1H), 10.37 (s, 1H), 10.53 (s, 1H). (m/z)=471 (M+H)+.

Workup

  1. additionwas added
  2. customQuenched with a saturated solution of NaHCO3
  3. extractionextracted twice with EtOAc
  4. washOrganic layer was washed with brine
  5. customdried
  6. customevaporated
  7. customPurification by HPLC

Sources & evidence

ORD record
ord-f81a6db70f7c41949555d30baa5a3079
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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