Dimethylamine, hydrochloride → N-(5-(2-(dimethylamino)isonicotinamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184841Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][N:29]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH3:26])=[C:12]([NH:14][C:15]([C:17]2[S:25][C:20]3=[N:21][CH:22]=[CH:23][N:24]=[C:19]3[CH:18]=2)=[O:16])[CH:13]=1)=[O:6].Cl.[CH3:31][NH:32][CH3:33]>C(O)C>[CH3:31][N:32]([CH3:33])[C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][N:29]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH3:26])=[C:12]([NH:14][C:15]([C:17]2[S:25][C:20]3=[N:21][CH:22]=[CH:23][N:24]=[C:19]3[CH:18]=2)=[O:16])[CH:13]=1)=[O:6]

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of N-(5-(2-bromoisonicotinamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 30 (25 mg, 0.053 mmol) in ethanol (1 mL) was added dimethylamine HCl (24.07 mg, 0.534 mmol) and TEA (10 eq). The resulting mixture was heated at 80° C. overnight and 2 h at 150° C. in microwave. Quenched in 3% citric acid solution and extracted with CH2Cl2 (2×). The combined organic layers were dried with Na2SO4 and evaporated. Triturating with ethyl acetate/heptane gave the title compound N-(5-(2-(dimethylamino)isonicotinamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 31a (11.3 mg, 49%). NMR (400 MHz, DMSO-d6) 2.26 (s, 3H), 3.11 (s, 6H), 7.03 (d, J=5.1 Hz, 1H), 7.10 (br s, 1H), 7.31 (d, J=8.2 Hz, 1H), 7.63 (dd, J=8.2 and 1.9 Hz, 1H), 7.87 (d, J=1.9 Hz, 1H), 8.23 (d, J=5.1 Hz, 1H), 8.56 (br s, 1H), 8.76 (d, J=2.3 Hz, 1H), 8.89 (d, J=2.3 Hz, 1H), 10.39 (br s, 1H), 10.54 (br s, 1H). (m/z)=433 (M+H)+.

Workup

customQuenched in 3% citric acid solution
extractionextracted with CH2Cl2 (2×)
dry with materialThe combined organic layers were dried with Na2SO4
customevaporated
customTriturating with ethyl acetate/heptane

Sources & evidence

ORD record: ord-490faec3331d4d67a6f949b2039b3249
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669256B2

Reaction notes

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