Water → HCID 57989824, compound

HRID 1962024Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:37])=[C:21]([NH:25][S:26]([C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.O.[CH3:39][N:40](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:39]([C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:37])=[C:21]([NH:25][S:26]([C:29]3[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1)#[N:40]

Participants

Conditions

Temperature: 60 °C

Procedure

N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (3.54 g, 6.23 mmol), zinc cyanide (0.805 g, 6.86 mmol), and tetrakis(triphenylphosphine)palladium (0) (0.720 g, 0.623 mmol) were stirred in N,N-dimethylformamide (DMF) (27.1 ml) overnight at 80° C. The reaction mixture was added dropwise into water to give a solid. The solids were filtered and dried in a vacuum oven overnight. DCM and MeOH (5:1) were added to solid and heat at 60° C. The mixture was cooled and filtered to obtain N-{3-[5-(2-cyano-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluorobenzenesulfonamide (2.06, 60%). MS (ESI): 559 [M+H]+.

Workup

customto give a solid
filtrationThe solids were filtered
customdried in a vacuum oven overnight
additionDCM and MeOH (5:1) were added to solid
temperatureThe mixture was cooled
filtrationfiltered

Sources & evidence

ORD record: ord-9e79b59fafe5422585d7c2625eb1b155
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415345B2

Reaction notes

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