HCID 57545954, compound → HCID 57546052, compound

HRID 913812Notes

Reaction equation

C[N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:33]([F:36])([F:35])[F:34])=[CH:8][C:9]=2[CH2:11][O:12][CH2:13][C:14]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH:4]=[N:3]1.CN1C=C2C(C(COCC3(C4C=CC=CC=4)CCN(C(OC(C)(C)C)=O)CC3)=CC(C(F)(F)F)=C2)=N1>>[C:27]1([C:14]2([CH2:13][O:12][CH2:11][C:9]3[CH:8]=[C:7]([C:33]([F:34])([F:36])[F:35])[CH:6]=[C:5]4[C:10]=3[NH:2][N:3]=[CH:4]4)[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])[CH2:18][CH2:19]2)[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

Reactant 2

HCID 57545954HCID 57545954, compound

HCID 57546205HCID 57546205, compound

Product 1

HCID 57546052HCID 57546052, compound

Procedure

tert-Butyl 4-(((1-methyl-5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate and tert-Butyl 4-(((2-methyl-5-(trifluoromethyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate. To a solution of tert-butyl 4-phenyl-4-(((5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate (350 mg, 0.715 mmol) in dimethylformamide (4 mL) at 0° C. was added sodium hydride (60% in mineral oil, 57.2 mg, 1.43 mmol). After 5 min, the reaction was treated with iodomethane (0.089 mL, 1.43 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-(((1-methyl-5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (187 mg, 52%). The second fraction was concentrated to give tert-butyl 4-(((2-methyl-5-(trifluoromethyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (76.5 mg, 21%). tert-Butyl 4-(((1-methyl-5-(trifluoromethyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 7.98 (s, 1H), 7.93 (s, 1H), 7.30 (s, 1H), 7.22 (m, 4H), 7.17 (m, 1H), 4.66 (s, 2H), 3.91 (s, 3H), 3.67 (m, 2H), 3.45 (s, 2H), 3.00 (m, 2H), 2.13 (m, 2H), 1.77 (m, 2H), 1.41 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.0, 142.6, 139.4, 133.9, 128.5, 127.1, 126.5, 124.8, 124.7 (q, J=272 Hz), 124.5, 122.5 (q, J=33 Hz), 121.1, 119.7 (q, J=3.8 Hz), 79.4, 79.2, 70.7, 41.5, 40.0 (br), 38.2, 32.2, 28.5. tert-Butyl 4-(((2-methyl-5-(trifluoromethyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 7.98 (s, 1H), 7.88 (s, 1H), 7.42 (m, 2H), 7.37 (m, 2H), 7.29 (s, 1H), 7.25 (m, 1H), 4.85 (s, 2H), 4.22 (s, 3H), 3.76 (m, 2H), 3.58 (s, 2H), 3.09 (m, 2H), 2.24 (m, 2H), 1.97 (m, 2H), 1.46 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 147.6, 142.9, 129.2, 128.5, 127.3, 126.4, 125.6, 124.9 (q, J=272 Hz), 124.1 (q, J=33 Hz), 120.7, 118.7, 117.6 (q, J=4.8 Hz), 79.9, 79.3, 68.7, 41.9, 40.7, 40.0 (br), 32.0, 28.6.

Sources & evidence

ORD record: ord-6d84bd3aa5eb414ba37b587b4fa4ec6c
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026257B2

Reaction notes

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