HCID 57546001, compound → HCID 57545968, compound

HRID 913804Notes

Reaction equation

C[N:2]1[C:10]2[C:5](=[CH:6][C:7]([CH3:33])=[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)=C2)=N1>>[CH3:33][C:7]1[CH:6]=[C:5]2[C:10](=[C:9]([CH2:11][O:12][CH2:13][C:14]3([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])[CH2:16][CH2:15]3)[CH:8]=1)[NH:2][N:3]=[CH:4]2

Participants

Reactant 2

HCID 57546001HCID 57546001, compound

HCID 57546124HCID 57546124, compound

Product 1

HCID 57545968HCID 57545968, compound

Procedure

tert-Butyl 4-(((1,5-dimethyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate and tert-Butyl 4-(((2,5-dimethyl-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate. To a solution of tert-butyl 4-(((5-methyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (38 mg, 0.087 mmol) in dimethylformamide (1 mL) at 0° C. was added sodium hydride (60% in mineral oil, 7.0 mg, 0.174 mmol). After 5 min, the reaction was treated with iodomethane (11 μL, 0.174 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 (2×), 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-(((1,5-dimethyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (24 mg, 61%). Concentration of the second fraction gave tert-butyl 4-(((2,5-dimethyl-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (8 mg, 20%). tert-Butyl 4-(((1,5-dimethyl-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 7.81 (s, 1H), 7.39 (s, 1H), 7.15-7.30 (m, 5H), 6.92 (s, 1H), 4.63 (s, 2H), 3.90 (s, 3H), 3.65 (bs, 2H), 3.41 (s, 2H), 3.00 (m, 2H), 2.39 (s, 3H), 2.10 (m, 2H), 1.79 (m, 2H), 1.41 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 142.9, 137.3, 132.1, 130.8, 129.3, 128.5, 127.2, 126.4, 126.0, 120.6, 119.8, 79.4, 78.7, 71.3, 41.5, 40.1 (br), 38.0, 32.1, 28.6, 21.0. tert-Butyl 4-(((2,5-dimethyl-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate: 1H-NMR (CDCl3, 500 MHz) δ 7.72 (s, 1H), 7.30-7.43 (m, 4H), 7.22 (m, 2H), 6.84 (s, 1H), 4.81 (s, 2H), 4.15 (s, 3H), 3.71 (bs, 2H), 3.53 (s, 2H), 3.06 (m, 2H), 2.32 (s, 3H), 2.17 (m, 2H), 1.97 (m, 2H), 1.43 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 146.3, 143.3, 131.0, 128.5, 127.4, 127.1, 126.3, 125.7, 122.9, 122.5, 117.0, 79.4, 79.3, 69.1, 41.9, 40.3, 40.2 (br), 32.0, 28.6, 21.9.

Sources & evidence

ORD record: ord-0fd1deb9167f4180a7826da13772a057
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026257B2

Reaction notes

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