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

HRID 1184833Notes

Reaction equation

HRID 1184833 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:33])[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([C:31]#[N:32])([CH3:30])[CH3:29])[CH:23]=4)[CH:17]=[CH:16][C:15]=3[CH3:34])=[O:12])[S:8][C:5]2=[N:6][CH:7]=1.[N:35]1[CH:40]=[CH:39][CH:38]=[C:37](B(O)O)[CH:36]=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>CCC(O)C.CCOC(C)=O.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]>[C:31]([C:28]([C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=1)[C:21]([NH:20][C:18]1[CH:17]=[CH:16][C:15]([CH3:34])=[C:14]([NH:13][C:11]([C:9]2[S:8][C:5]3=[N:6][CH:7]=[C:2]([C:37]4[CH:36]=[N:35][CH:40]=[CH:39][CH:38]=4)[N:3]=[C:4]3[CH:10]=2)=[O:12])[CH:19]=1)=[O:33])([CH3:30])[CH3:29])#[N:32]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 547564232-chloro-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

Product 1

HCID 86680167N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-2-(pyridin-3-yl)thieno[2,3-b]pyrazine-6-carboxamideYield 27.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6568(+-)-2-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 24 (30 mg, 0.061 mmol), pyridine-3-boronic acid (11.2 mg, 0.092 mmol), tris(dibenzylideneacetone)dipalladium(0) (2.8 mg, 3.06 μmol), potassium phosphate, tribasic (26 mg, 0.122 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (2.92 mg, 6.12 μmol) in butanol-2-ol was stirred at 100° C. for 30 min. Diluted with EtOAc and washed with water, brine, dried and evaporated. Triturating with acetonitrile gave the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)-2-(pyridin-3-yl)thieno[2,3-b]pyrazine-6-carboxamide 25h (9 mg, 27.6%). NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 2.29 (s, 3H), 7.33 (d, J=8.2 Hz, 1H), 7.58-7.69 (m, 3H), 7.76 (d, J=7.8 Hz, 1H), 7.90 (s, 1H), 7.96 (d, J=7.8 Hz, 1H), 8.06 (s, 1H), 8.62 (m, 2H), 8.76 (d, J=4.7 Hz, 1H), 9.45 (m, 2H), 10.38 (s, 1H), 10.55 (s, 1H). (m/z)=533 (M+H)+.

Workup

  1. washwashed with water, brine
  2. customdried
  3. customevaporated
  4. customTriturating with acetonitrile

Sources & evidence

ORD record
ord-30e9f91cdc4f484ea14f497e81f60bfa
Source dataset
uspto-grants-2014_03
Patent number
US08669256B2

Reaction notes

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