Sodium hydride → 1-[4-(7-Chloro-1-methoxy-isoquinolin-6-yloxy)-1-trifluoromethyl-cyclohexyl]-propylamine
Reaction equation
[H-].[Na+].[NH2:3][CH:4]([C:7]1([C:14]([F:17])([F:16])[F:15])[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]1)[CH2:5][CH3:6].[Cl:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[CH:24][N:25]=[C:26]2[O:29][CH3:30])=[CH:21][C:20]=1F.C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[Cl:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[CH:24][N:25]=[C:26]2[O:29][CH3:30])=[CH:21][C:20]=1[O:13][CH:10]1[CH2:11][CH2:12][C:7]([CH:4]([NH2:3])[CH2:5][CH3:6])([C:14]([F:15])([F:16])[F:17])[CH2:8][CH2:9]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
160 mg (4.00 mmol) of NaH were suspended using 3 ml of DMA and a solution of 300 mg (1.33 mmol) of 4-(1-Amino-propyl)-4-trifluoromethyl-cyclohexanol (74) in 3 ml of DMA added. The mixture was stirred for 1 h at ambient temperature. Afterwards, a solution of 282 mg (1.33 mmol) of 7-chloro-6-fluoro-1-methoxy-isoquinoline in 4 ml of DMA was added and the mixture was stirred for 3 h at ambient temperature. The mixture was then poured into 100 ml of a saturated aqueous solution of NaHCO3 and extracted three times using 50 ml of ethyl acetate each. The organic layer was washed twice using 50 ml of water, dried using MgSO4 and evaporated. Chromatography on silica gel using ethyl acetate/n-heptane, followed by chromatography on silica gel using t-butylmethyl ether/n-heptane 1:1+1% acetic acid yielded 162 mg of the desired product as the acetate. Rt=0.77 min (Method P).
Workup
- stirringthe mixture was stirred for 3 h at ambient temperature
- extractionextracted three times
- washThe organic layer was washed twice
- customdried
- customevaporated
Sources & evidence
- ORD record
- ord-8a2d633e6ac54cffb9d00ab7a792abe1
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08399482B2
Reaction notes
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