Ethanamine, 2,2,2-trifluoro- → 3-(1-(4-Fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl 2,2,2-trifluoroethylcarbamate

HRID 218184Notes

Reaction equation

HRID 218184 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:18]([CH3:22])([CH3:21])[CH2:19][OH:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[C:29](C1NC=CN=1)(C1NC=CN=1)=[O:30].[F:41][C:42]([F:46])([F:45])[CH2:43][NH2:44]>C1COCC1.CN(C)C1C=CN=CC=1>[F:41][C:42]([F:46])([F:45])[CH2:43][NH:44][C:29](=[O:30])[O:20][CH2:19][C:18]([CH3:22])([CH3:21])[CH:17]([C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[N:9]=[CH:10]2)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 9773Ethanamine, 2,2,2-trifluoro-2×HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 687058683-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-ol

Product 1

HCID 687076873-(1-(4-Fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl 2,2,2-trifluoroethylcarbamateYield 10%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

3-(1-(4-Fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-ol (prepared from LiAlH4 reduction of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoate in Example 1(g)) (37 mg) in THF (1 ml) was treated with carbonyl diimidazole (29 mg, 0.176 mmol) at room temperature overnight. To the reaction solution was added 2,2,2-trifluoroethanamine (26 mg, 0.264 mmol). The reaction was heated at 50° C. for 14 hours. Additional 2,2,2-trifluoroethanamine 26 mg, 0.264 mmol) was added followed by addition of N,N-dimethylpyridin-4-amine (10 mg, 0.080 mmol), after which stirring was continued for 14 hours. The reaction was concentrated. The crude material was purified via chromatography on silica gel eluting with 10% ethyl acetate in hexane to afford the compound of Example 14 (4 mg, 10% yield). 1H NMR (400 MHz, MeOD) δ ppm 8.20 (1 H, s) 7.97 (1 H, s) 7.71 (2 H, dd, J=9.16, 4.58 Hz) 7.63 (2 H, s) 7.54 (2 H, d, J=7.12 Hz) 7.26-7.34 (4 H, m) 7.19 (1 H, t, J=7.38 Hz) 4.26 (1 H, s) 3.73-3.82 (4 H, m) 1.11 (6 H, d, J=3.05 Hz). LC/MS (m/z) 500.29 [(M+H)+]; HPLC Rt: 3.871 min.

Workup

  1. concentrationThe reaction was concentrated
  2. customThe crude material was purified via chromatography on silica gel eluting with 10% ethyl acetate in hexane

Sources & evidence

ORD record
ord-ca8a850ddf10470a8c636588fa15aed8
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

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