Trifluoroacetic acid → (R)-5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid

HRID 927275Notes

Reaction equation

HRID 927275 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:24]([CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O:31]C(C)(C)C)=[O:30])=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:36]([N:38]4[CH2:43][CH2:42][N:41]([C:44]5[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=5)[CH2:40][C@H:39]4[CH3:51])=[O:37])[CH:21]=3)[C:16]2=[O:52])=[CH:11][CH:10]=1>ClCCl>[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:24]([CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:36]([N:38]4[CH2:43][CH2:42][N:41]([C:44]5[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=5)[CH2:40][C@H:39]4[CH3:51])=[O:37])[CH:21]=3)[C:16]2=[O:52])=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90094332(R)-tert-butyl 5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

Product 1

HCID 90095410(R)-5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acidYield 87.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1 mL, 12.98 mmol) was added to a stirred, room temperature mixture of (R)-tert-butyl 5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (58 mg, 0.094 mmol) in dichloromethane (4 mL) and the mixture was stirred at room temperature for 2 hours. The mixture was concentrated to dryness, the residue was purified via PTLC (Emerck 1 mm), eluted with CH2Cl2/MeOH=10:1 to give (R)-5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid (46 mg, 0.082 mmol) as a light yellow solid. LCMS [M+H]+=560. 1H NMR (500 MHz, CDCl3) δ ppm: 8.43 (d, J=8.28 Hz, 1H), 7.56 (d, J=1.32 Hz, 1H), 7.44 (dd, J=8.28, 1.32 Hz, 1H), 7.26 (m, 2H), 7.25 (m, 2H), 6.96-7.07 (m, 2H), 6.86-6.93 (m, 2H), 6.48 (s, 1H), 3.52 (m, 3H), 2.96 (m, 1H), 2.79 (m, 1H), 2.31 (m, 4H), 1.55-1.68 (m, 6H), 1.50 (d, 3H).

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. customthe residue was purified via PTLC (Emerck 1 mm)
  3. washeluted with CH2Cl2/MeOH=10:1

Sources & evidence

ORD record
ord-346fe2d2e61f4e0c9b98127edc3d7229
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

Loading…