(R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline → (R)-N-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)-phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

HRID 445379Notes

Reaction equation

[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.[I-].[O:22]=[C:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25](=[O:32])[N:24]1[CH2:33][CH2:34][N:35]([C:44]1[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=1)[C:36](N1C=C[N+](C)=C1)=[O:37]>C(Cl)Cl>[O:32]=[C:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:23](=[O:22])[N:24]1[CH2:33][CH2:34][N:35]([C:44]1[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=1)[C:36]([N:10]1[CH2:11][CH2:12][C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@H:9]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:8][CH:7]=1)=[O:37]

Participants

Conditions

Temperature: 40 °C

Procedure

To a 50 mL round-bottomed flask was added (R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (80 mg, 290 μmol), 1-((2-(1,3-dioxoisoindolin-2-yl)ethyl)(4-fluorophenyl)carbamoyl)-3-methyl-1H-imidazol-3-ium iodide (151 mg, 290 μmol, from step 3), CH2Cl2 (2 mL). The reaction mixture was stirred at 40° C. for 48 h. The solvent was removed in vacuo and the residue was purified by silica gel chromatography, eluting with 30% EtOAc/hexanes to give (R)—N-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-N-(4-fluorophenyl)-1-(4-(trifluoromethyl)-phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide. MS (ESI pos. ion) m/z: 588 (M+1).

Workup

customThe solvent was removed in vacuo
customthe residue was purified by silica gel chromatography
washeluting with 30% EtOAc/hexanes

Sources & evidence

ORD record: ord-a29c271e0b3d4a76ba899e8a86ad401e
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08476297B2

Reaction notes

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