Tetrahydrofuran → (2R)-2-(5-(2-(3,4-Dichlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-hydroxy-N-methylpropanamide

Reaction equation

[Si]([O:8][CH2:9][C@@H:10]([N:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][C:21]=2[NH:25][C:26](=[O:37])[CH:27]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=2)[CH3:28])[C:16]1=[O:38])[C:11]([NH:13][CH3:14])=[O:12])(C(C)(C)C)(C)C.O1CCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[Cl:36][C:31]1[CH:30]=[C:29]([CH:27]([CH3:28])[C:26]([NH:25][C:21]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:22]=2[CH:23]=[CH:24][N:15]([C@H:10]([CH2:9][OH:8])[C:11]([NH:13][CH3:14])=[O:12])[C:16]3=[O:38])=[O:37])[CH:34]=[CH:33][C:32]=1[Cl:35]

Participants

Reactant 3

HCID 8028Tetrahydrofuran

HCID 2724141Tetrabutylammonium Fluoride

HCID 58973958(2R)-3-(tert-Butyldimethylsilyloxy)-2-(5-(2-(3,4-dichlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-N-methylpropanamide

Product 1

HCID 52914241(2R)-2-(5-(2-(3,4-Dichlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-hydroxy-N-methylpropanamide

Procedure

A round bottom flask was charged with (2R)-3-(tert-butyldimethylsilyloxy)-2-(5-(2-(3,4-dichlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-N-methylpropanamide (60 mg, 0.0001 mol), tetrahydrofuran (3 mL, 0.04 mol) and tetra-n-butylammonium fluoride (0.037 mL, 0.00012 mol) and the reaction stirred at room temperature for 30 minutes during which time the reaction was complete. The solvent was removed under reduced pressure and the residue purified by preparative HPLC (reverse phase) to yield the product as a white solid. MS m/z=463.3 (M+H). 1H NMR (400 MHz; DMSO-d6) δ 10.02 (s, 1H), 8.12 (m, 1H), 8.06 (d, J=8.26 Hz, 1H), 7.74 (t, J=7.29 Hz, 1H), 7.68 (d, J=1.82 Hz, 1H), 7.64 (d, J=8.43 Hz, 1H), 7.51 (dd, J=7.97&3.17 Hz, 1H), 7.46-7.42 (m, 2H), 6.37 (dd, J=5.04&2.04 Hz, 1H), 5.47 (t, J=6.94 Hz, 1H), 5.15-5.13 (m, 1H), 4.05 (q, J=7.24 Hz, 1H), 3.95-3.92 (m, 2H), 2.57 (d, J=4.25 Hz, 3H), 1.47 (d, J=7.22 Hz, 3H).