Tert-butyl 7-amino-4,5-dihydro-1H-benzo[D]azepine-3(2H)-carboxylate → 7-[5-(2-Methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester

HRID 1890004Notes

Reaction equation

HRID 1890004 reaction equation
Cl[C:2]1[N:22]=[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]3[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=3[O:20][CH3:21])[N:4]2[N:3]=1.[C:23]([O:27][C:28]([N:30]1[CH2:36][CH2:35][C:34]2[CH:37]=[CH:38][C:39]([NH2:41])=[CH:40][C:33]=2[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>>[C:23]([O:27][C:28]([N:30]1[CH2:36][CH2:35][C:34]2[CH:37]=[CH:38][C:39]([NH:41][C:2]3[N:22]=[C:5]4[CH:6]=[CH:7][CH:8]=[C:9]([C:10]5[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=5[O:20][CH3:21])[N:4]4[N:3]=3)=[CH:40][C:33]=2[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

3

Reactant 2

HCID 11402789Tert-butyl 7-amino-4,5-dihydro-1H-benzo[D]azepine-3(2H)-carboxylateHCID 674791232-Chloro-5-(2-methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 674815237-[5-(2-Methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester

Procedure

2-Chloro-5-(2-methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine was prepared from 8-bromo-2-chloro[1,2,4]triazolo[1,5-a]pyridine (0.5 g, 2.15 mmol) and 2-methoxy-5-trifluoromethylbenzeneboronic acid (0.71 g, 3.23 mmol) in a manner analogous to Example 2c. Product was isolated as a foam (0.7 g, 82%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.80 (d, J=8.8 Hz, 1H), 7.75-7.70 (m, 2H), 7.68-7.62 (m, 1H), 7.16 (d, J=8.8 Hz, 1H), 7.09 (d, J=6.8 Hz, 1H), 3.87 (s, 3H). MS=328 (MH)+. 234b) 7-[5-(2-Methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester was prepared from 2-chloro-5-(2-Methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.46 g, 1.4 mmol) and 7-amino-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.557 g, 2.12 mmol) in a manner analogous to Example 2d. Product was isolated as a foam (0.33 g, 42%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.94 (brs, 1H), 7.80-7.77 (m, 1H), 7.55-7.49 (m, 2H), 7.20-7.15 (m, 1H), 7.05-7.00 (m, 1H), 7.00-6.96 (m, 1H), 6.90 (brs, 1H), 3.88 (s, 3H), 3.60-3.48 (m, 4H), 2.89-2.78 (m, 4H), 1.52 (s, 9H). MS=554 (MH)+. 234c) 7-[5-(2-Methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.33 g, 6.00 mmol), was dissolved in dichloromethane (10 mL, 156 mmol) and trifluoroacetic acid was added (2 mL, 20.0 mmol). Reaction was stirred at room temperature for 2 hours. Solvent was removed and residue was partitioned between dichloromethane and 1N sodium carbonate. Washed with water and brine, dried over sodium sulfate and concentrated. [5-(2-Methoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amino]-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-amine was isolated as a foam (0.27 g, 96%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.94 (brs, 1H), 7.81-7.76 (m, 1H), 7.54-7.50 (m, 2H), 7.25 (brs, 1H), 7.17 (d, J=7.9 Hz, 1H), 7.02 (d, J=7.9 Hz, 1H), 6.99-6.95 (m, 1H), 6.83 (brs, 1H), 3.86 (s, 3H), 3.01-2.92 (m, 4H), 2.90-2.83 (m, 4H). MS=454 (MH)+.

Sources & evidence

ORD record
ord-e073730e0ef64fb8abfa75a35e058501
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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