Oxonium, triethyl-, hexafluorophosphate(1-) (1:1) → (S)-methyl 5-(tert-butoxycarbonyl(methyl)amino)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoate
Reaction equation
[N:1]1([C:6]([O:8][CH2:9][C@@H:10]([N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH3:19])[CH2:11][CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])=[O:7])[CH:5]=[CH:4][N:3]=[CH:2]1.F[P-](F)(F)(F)(F)F.C([O+](CC)CC)C.C1C2[C:45](=[CH:46][CH:47]=[CH:48]C=2)[CH:44]=[C:43](N)N=1>C(Cl)Cl>[C:23]([O:22][C:20]([N:18]([CH3:19])[C@H:10]([CH2:9][O:8][C:6](=[O:7])[NH:1][C:2]1[N:3]=[CH:4][C:5]2[C:47]([CH:48]=1)=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:11][CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])=[O:21])([CH3:24])([CH3:25])[CH3:26]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of (S)-2-(tert-butoxycarbonyl(methyl)amino)-6-methoxy-6-oxohexyl 1H-imidazole-1-carboxylate (2 g, 5.4 mmol) in DCM (10 mL) was added a solution of triethyloxonium hexafluorophosphate (1.61 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) dropwise at 0° C. The solution was warmed up to RT and stirred for 15 min. A solution of isoquinolin-3-amine (0.94 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) was added. The solution was stirred for overnight. DCM was removed and the residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-methyl 5-(tert-butoxycarbonyl(methyl)amino)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoate (1.4 g, 58%). LRMS (M+H+) m/z 446.2.
Workup
- stirringThe solution was stirred for overnight
- customDCM was removed
- customthe residue was purified on RP-HPLC
- additiona mixture of acetonitrile and H2O
Sources & evidence
- ORD record
- ord-2f29a33861314c9e808309d9b892d36c
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08088793B2
Reaction notes
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