Sodium Carbonate → 5-chloro-4-(1,4-dimethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide

HRID 2392018Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]([NH:10][C@@H:11]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([F:34])([F:33])[F:32])[CH2:12][N:13]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[O:9])[S:5][C:6]=1[Cl:7].C([O-])([O-])=O.[Na+].[Na+].[CH3:41][N:42]1[C:46](B2OC(C)(C)C(C)(C)O2)=[C:45]([CH3:56])[CH:44]=[N:43]1>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:7][C:6]1[S:5][C:4]([C:8]([NH:10][C@@H:11]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([F:34])([F:33])[F:32])[CH2:12][N:13]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[O:9])=[CH:3][C:2]=1[C:46]1[N:42]([CH3:41])[N:43]=[CH:44][C:45]=1[CH3:56]

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of 4-bromo-5-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide (260 mg, 0.46 mmol) in THF (5 mL) was added Na2CO3 (2N, 0.7 mL, 1.4 mmol), Pd(dppf)Cl2 (40 mg, 48 μmol) and 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (303 mg, 1.38 mmol). The reaction mixture was heated to 75° C. in a sealed tube under N2. After 8 h, the reaction mixture was concentrated under vacuum and purified on silica (10:1 CHCl3/MeOH) to afford the title compound (196 mg, 73.4%): LC-MS (ES) m/z=587 (M+H)+.

Workup

concentrationthe reaction mixture was concentrated under vacuum
custompurified on silica (10:1 CHCl3/MeOH)

Sources & evidence

ORD record: ord-59cbfe1bf4af40c79404a3aaa2bb99fa
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273782B2

Reaction notes

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