Dimethylformamide → N-(2-((R)-1-Amino-1-oxopropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(4-chloro-3-(trifluoromethyl)phenyl)propanamide

HRID 1161219Notes

Reaction equation

HRID 1161219 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]([C@H:13]([CH3:17])[C:14]([NH2:16])=[O:15])[C:7]2=[O:12].CN(C)C=O.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]([CH3:34])[C:31](O)=[O:32])=[CH:26][C:25]=1[C:35]([F:38])([F:37])[F:36].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CCOC(C)=O>[NH2:16][C:14](=[O:15])[C@H:13]([N:6]1[CH:5]=[CH:4][C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[NH:1][C:31](=[O:32])[CH:30]([C:27]2[CH:28]=[CH:29][C:24]([Cl:23])=[C:25]([C:35]([F:36])([F:37])[F:38])[CH:26]=2)[CH3:34])[C:7]1=[O:12])[CH3:17]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 572006802-[4-Chloro-3-(trifluoromethyl)phenyl]propanoic acidHCID 59515719(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)propanamide

Product 1

HCID 52914339N-(2-((R)-1-Amino-1-oxopropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(4-chloro-3-(trifluoromethyl)phenyl)propanamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (R)-2-(5-amino-1-oxoisoquinolin-2(1H)-yl)propanamide (183.1 mg, 0.0007522 mol) in N,N-dimethylformamide (6 mL, 0.08 mol) was added 2-(4-chloro-3-(trifluoromethyl)phenyl)propanoic acid (110.0 mg, 0.0004137 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (360 mg, 0.00095 mol) and N,N-diisopropylethylamine (305 μL, 0.00175 mol). The reaction mixture was stirred at 50° C. overnight. LC/MS was checked, and the reaction was complete. In the work up, EtOAc (100 mL) was added to the reaction solution, and the solution was washed with water (2×100 mL), Sat. NaHCO3, H2O, and brine. The mixture was dried with MgSO4 and was rotovaped. The residue was purified by HPLC. The product was recovered as a solid. MS m/z=466.1 (M+1). 1H NMR (400 MHz; DMSO-d6) δ 10.08(s, 1 H), 8.07(d, J=7.9 Hz, 1 H), 7.92(s, 1 H), 7.80-70(m, 3 H), 7.63(s, 1 H), 7.50-7.40(m, 2 H), 7.23 (s, 1 H), 6.51(dd, J=7.6, 4.8 Hz, 1 H), 5.47(q, J=7.2 Hz, 1 H), 4.16(q, J=7.0 Hz, 1 H), 1.58-1.45(m, 6H).

Workup

  1. washthe solution was washed with water (2×100 mL), Sat. NaHCO3, H2O, and brine
  2. dry with materialThe mixture was dried with MgSO4
  3. customThe residue was purified by HPLC
  4. customThe product was recovered as a solid

Sources & evidence

ORD record
ord-4ea6574f287c429aa459f3c2b3a94165
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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