Potassium Phosphate, Tribasic → N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-2-(pyridin-3-yl)thieno[2,3-b]pyrazine-6-carboxamide

HRID 1184879Notes

Reaction equation

HRID 1184879 reaction equation
Cl[C:2]1[N:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([NH:20][C:21](=[O:32])[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=4)[CH:17]=[CH:16][C:15]=3[CH3:33])=[O:12])[S:8][C:5]2=[N:6][CH:7]=1.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CC(O)CC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:33][C:15]1[CH:16]=[CH:17][C:18]([NH:20][C:21](=[O:32])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)=[CH:19][C:14]=1[NH:13][C:11]([C:9]1[S:8][C:5]2=[N:6][CH:7]=[C:2]([C:36]3[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=3)[N:3]=[C:4]2[CH:10]=1)=[O:12]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866801752-chloro-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamide

Product 1

HCID 67125584N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-2-(pyridin-3-yl)thieno[2,3-b]pyrazine-6-carboxamideYield 9.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6568(+-)-2-ButanolSolvent

Procedure

A mixture of 2-chloro-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)thieno[2,3-b]pyrazine-6-carboxamide 68 (100 mg, 0.204 mmol), pyridine-3-boronic acid (37.6 mg, 0.306 mmol), potassium phosphate, tribasic (86 mg, 0.407 mmol), tris(dibenzylideneacetone)dipalladium(0) (9.33 mg, 10.19 μmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (9.71 mg, 0.020 mmol) in butane-2-ol was stirred was stirred at 100° C. for 30 min in microwave. Water was added and extracted with EtOAc. Organic layer was washed with water, brine, dried and evaporated. Crystallization with acetonitrile gave the title compound N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-2-(pyridin-3-yl)thieno[2,3-b]pyrazine-6-carboxamide 69 (10 mg, 9%). NMR (400 MHz, DMSO-d6) 2.29 (s, 3H), 7.33 (d, J=8.6 Hz, 1H), 7.65 (m, 2H), 7.80 (t, J=7.8 Hz, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.98 (d, J=8.2 Hz, 1H), 8.28 (d, J=7.8 Hz, 1H), 8.32 (s, 1H), 8.61 (s, 1H), 8.63 (t, J=1.6 Hz, 1H), 8.76 (dd, J=4.7 Hz and 1.6 Hz, 1H), 9.43 (d, J=2.0 Hz, 1H), 9.46 (s, 1H), 10.54 (s, 1H), 10.55 (s, 1H). (m/z)=535 (M+H)+.

Workup

  1. stirringwas stirred at 100° C. for 30 min in microwave
  2. extractionextracted with EtOAc
  3. washOrganic layer was washed with water, brine
  4. customdried
  5. customevaporated
  6. customCrystallization with acetonitrile

Sources & evidence

ORD record
ord-315399fc63634a47b9ff195b9f6ee0e2
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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