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

HRID 1161225Notes

Reaction equation

HRID 1161225 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

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 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).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue purified by preparative HPLC (reverse phase)

Sources & evidence

ORD record
ord-6b79c0cb31594958869d8b164c0ca881
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

Loading…