Ammonia → 6-(5-(Methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-7-ol
Reaction equation
C[O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[N:10]2)=[CH:5][C:4]=1[C:13]1[S:17][C:16]([N:18]([CH3:29])[CH:19]2[CH2:24][C:23]([CH3:26])([CH3:25])[NH:22][C:21]([CH3:28])([CH3:27])[CH2:20]2)=[N:15][N:14]=1.Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+].N>CO.C(Cl)Cl>[CH3:29][N:18]([CH:19]1[CH2:24][C:23]([CH3:26])([CH3:25])[NH:22][C:21]([CH3:28])([CH3:27])[CH2:20]1)[C:16]1[S:17][C:13]([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][C:3]=2[OH:2])[N:10]=[CH:9][CH:8]=[CH:7]3)=[N:14][N:15]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 160 °C
Procedure
A mixture of 5-(7-methoxyquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (30 mg, 0.073 mmol) and pyridine hydrochloride (126 mg, 1.093 mmol) was heated in a microwave at 160° C. for 30 minutes. The resulting solid was dissolved into methanol and concentrated onto a mixture of silica gel (500 mg) and sodium bicarbonate (14.6 mmol, 122 mg) and subjected to flash column chromatography (4 g silica gel, 1-17% 1.4 N ammonia in MeOH gradient in DCM over 30 column volumes) to provide 6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-7-ol as a yellow solid (24 mg, 83%). MS=398.3 (M+1). 1H NMR (400 MHz, METHANOL-d4) ppm 8.67 (d, J=3.0 Hz, 1H), 8.49 (s, 1H), 8.29 (d, J=7.6 Hz, 1H), 7.36 (s, 1H), 7.28 (dd, J=8.3, 4.3 Hz, 1H), 4.55 (t, J=12.1 Hz, 1H), 3.13 (s, 3H), 1.90 (dd, J=12.6, 3.0 Hz, 2H), 1.62-1.78 (m, 2H), 1.46 (s, 6H), 1.33 (s, 6H).
Sources & evidence
- ORD record
- ord-d82e12638d2c472b9a4577f5f042be1e
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09040712B2
Reaction notes
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