HCID 57546206, compound → HCID 57546006, compound

HRID 913814Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][O:22][CH2:23][C:24]3[CH:25]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:27]=[C:28]4[C:32]=3[N:31](C)[N:30]=[CH:29]4)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.FC1C=CC(C2(COCC3C4C(=CN(C)N=4)C=C(C(F)(F)F)C=3)CCN(C(OC(C)(C)C)=O)CC2)=CC=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][O:22][CH2:23][C:24]3[CH:25]=[C:26]([C:34]([F:35])([F:36])[F:37])[CH:27]=[C:28]4[C:32]=3[NH:31][N:30]=[CH:29]4)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

Reactant 2

HCID 57546206HCID 57546206, compound

HCID 57546251HCID 57546251, compound

Product 1

HCID 57546006HCID 57546006, compound

Procedure

tert-Butyl 4-(4-fluorophenyl)-4-(((1-methyl-5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate and tert-Butyl 4-(4-fluorophenyl)-4-(((2-methyl-5-(trifluoromethyl)-2H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate. To a solution of tert-butyl 4-(4-fluorophenyl)-4-(((5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate (115 mg, 0.227 mmol) in dimethylformamide (2 mL) at 0° C. was added sodium hydride (60% in mineral oil, 18.1 mg, 0.45 mmol). After 5 min, the reaction was treated with iodomethane (0.028 mL, 0.45 mmol). After 30 min, the reaction was quenched by addition of saturated ammonium chloride and poured into diethyl ether. The organics were washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→75% EtOAc/Hex) gave two fractions. The faster eluting fraction was concentrated to give tert-butyl 4-(4-fluorophenyl)-4-(((1-methyl-5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate (66 mg, 56%). The second fraction was concentrated to give tert-butyl 4-(4-fluorophenyl)-4-(((2-methyl-5-(trifluoromethyl)-2H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate (26 mg, 22%). tert-Butyl 4-(4-fluorophenyl)-4-(((1-methyl-5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 8.03 (s, 1H), 7.98 (s, 1H), 7.31 (s, 1H), 7.17 (m, 2H), 6.91 (m, 2H), 4.72 (s, 2H), 4.03 (s, 3H), 3.67 (m, 2H), 3.46 (s, 2H), 3.02 (m, 2H), 2.10 (m, 2H), 1.79 (m, 2H), 1.44 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 162.3, 160.3, 139.6, 135.4, 128.7, 128.6, 124.7 (q, J=272 Hz), 123.3 (q, J=32 Hz), 122.9, 121.8, 120.3 (q, J=2.9 Hz), 118.4 (q, J=4.8 Hz), 115.8, 115.6, 80.4, 71.9, 51.8, 46.3, 40.3, 32.9. tert-Butyl 4-(4-fluorophenyl)-4-(((2-methyl-5-(trifluoromethyl)-2H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.89 (s, 1H), 7.35 (m, 2H), 7.24 (s, 1H), 7.03 (m, 2H), 4.85 (s, 2H), 4.24 (s, 3H), 3.72 (m, 2H), 3.55 (s, 2H), 3.10 (m, 2H), 2.18 (m, 2H), 1.94 (m, 2H), 1.46 (s, 9H); 3C-NMR (CDCl3, 126 MHz) δ 162.4, 160.5, 155.1, 147.6, 138.7, 129.0, 128.9, 128.8, 125.6, 124.8 (q, J=273 Hz), 124.1 (q, J=32 Hz), 120.8, 118.8, 117.7 (q, J=4.8 Hz), 115.3, 115.1, 79.6, 79.4, 68.7, 41.4, 40.7, 40.2 (br), 32.2, 28.5.

Sources & evidence

ORD record: ord-03fd3b26114a41a0b0a34341a8395d94
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026257B2

Reaction notes

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