Cesium carbonate → N-[(1S)-2-phenyl-1-(1-phenylimidazol-2-yl)ethyl]-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]acetamide

HRID 1506618Notes

Reaction equation

HRID 1506618 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C@@H:6]([NH:14][C:15](=[O:30])[CH2:16][N:17]1[C:25]2[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=2[C:19]([C:26]([F:29])([F:28])[F:27])=[N:18]1)[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.I[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN1C(=O)CCC1>[C:8]1([CH2:7][C@H:6]([NH:14][C:15](=[O:30])[CH2:16][N:17]2[C:25]3[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=3[C:19]([C:26]([F:27])([F:28])[F:29])=[N:18]2)[C:2]2[N:1]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:5]=[CH:4][N:3]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 11575IodobenzeneHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 90281449(S)-N-(1-(1H-imidazol-2-yl)-2-phenylethyl)-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamide

Product 1

HCID 90281303N-[(1S)-2-phenyl-1-(1-phenylimidazol-2-yl)ethyl]-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl]acetamide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
115 °C

Procedure

To (S)-N-(1-(1H-imidazol-2-yl)-2-phenylethyl)-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamide (111 mg, 0.27 mmol) in NMP (0.6 mL) was added iodobenzene (27 μL, 0.24 mmol), Cu2O (1 mg), PEG 3500 (50 mg), 4,7-dimethoxy-1,10-phenanthroline (6 mg) and Cs2CO3 (110 mg, 0.34 mmol). The reaction was heated to 115° C. for 4 hr. After cooling to ambient temperature, the reaction mixture was filtered over a heavy metal scavenging column and eluted with DCM. The solvents were removed in vacuo and the residue purified by RP HPLC to provide the title compound: 1H NMR (400 MHz, DMSO-d6) δ 9.16 (s), 7.55 (s, 1H), 7.42 (t, 1H), 7.14 (q, 2H), 7.01 (d, 1H), 6.84 (dd, 1H), 4.77-4.71 (m, 1H), 3.08 (d, 1H), 2.36 (s, 1H), 1.62 (d, 2H). MS (m/z) 494.3 [M+H]+.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. filtrationthe reaction mixture was filtered over a heavy metal scavenging column
  3. washeluted with DCM
  4. customThe solvents were removed in vacuo
  5. customthe residue purified by RP HPLC

Sources & evidence

ORD record
ord-e936c42639fa499c9b780e561dff5e55
Source dataset
uspto-grants-2015_12
Patent number
US09220710B2

Reaction notes

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