Pyrrolidine → N-(2-methyl-5-(2-(pyrrolidin-1-yl)isonicotinamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184842Notes

Reaction equation

HRID 1184842 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].[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>>[CH3:26][C:11]1[CH:10]=[CH:9][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:27]=[CH:28][N:29]=[C:2]([N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)[CH:3]=2)=[CH:13][C:12]=1[NH:14][C:15]([C:17]1[S:25][C:20]2=[N:21][CH:22]=[CH:23][N:24]=[C:19]2[CH:18]=1)=[O:16]

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 86680169N-(5-(2-bromoisonicotinamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

Product 1

HCID 54754634N-(2-methyl-5-(2-(pyrrolidin-1-yl)isonicotinamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamideYield 44%

Conditions

Temperature
80 °C

Procedure

A mixture of N-(5-(2-bromoisonicotinamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 30 (25 mg, 0.053 mmol) in pyrrolidine (0.5 mL) was heated at 80° C. overnight. Quenched in 3% citric acid solution and extracted with CH2Cl2 (2×). The combined organic layers were dried with Na2SO4 and concentrated in vacuo. Purification by chromatography CH2Cl2/MeOH (97/3) and triturating with acetonitrile gave the title compound N-(2-methyl-5-(2-(pyrrolidin-1-yl)isonicotinamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamide 31b (10.7 mg, 44%). NMR (400 MHz, DMSO-d6) 1.97 (m, 4H), 2.26 (s, 3H), 3.45 (m, 4H), 6.88 (s, 1H), 6.98 (dd, J=5.1 and 1.2 Hz, 1H), 7.30 (d, J=8.6 Hz, 1H), 7.62 (dd, J=8.23 and 1.6 Hz, 1H), 7.87 (d, J=2.3 Hz, 1H), 8.21 (d, J=5.1 Hz, 1H), 8.53 (br s, 1H), 8.75 (d, J=2.3 Hz, 1H), 8.88 (d, J=2.3 Hz, 1H), 10.33 (s, 1H), 10.52 (s, 1H). (m/z)=459 (M+H)+.

Workup

  1. customQuenched in 3% citric acid solution
  2. extractionextracted with CH2Cl2 (2×)
  3. dry with materialThe combined organic layers were dried with Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification by chromatography CH2Cl2/MeOH (97/3)
  6. customtriturating with acetonitrile

Sources & evidence

ORD record
ord-ac9535772dc34474b44fa4c966290830
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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