Sodium Hydroxide → 2-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(2-(1,3-dihydroxypropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)acetamide

HRID 1161192Notes

Reaction equation

HRID 1161192 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]([CH:13]([CH2:16][OH:17])[CH2:14][OH:15])[C:7]2=[O:12].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26](O)=[O:27])=[CH:21][C:20]=1[C:29]([F:32])([F:31])[F:30].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.[OH-].[Na+]>CCOC(C)=O.CO.CN(C=O)C>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]([NH:1][C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]([CH:13]([CH2:14][OH:15])[CH2:16][OH:17])[C:7]3=[O:12])=[O:27])=[CH:21][C:20]=1[C:29]([F:30])([F:31])[F:32]

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 35198824-Chloro-3-(trifluoromethyl)phenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595157945-Amino-2-(1,3-dihydroxypropan-2-yl)isoquinolin-1(2H)-one

Product 1

HCID 247608102-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(2-(1,3-dihydroxypropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)acetamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-amino-2-(1,3-dihydroxypropan-2-yl)isoquinolin-1(2H)-one (100.0 mg, 0.0004055 mol) in N,N-dimethylformamide (8 mL, 0.1 mol) was added 2-(4-chloro-3-(trifluoromethyl)phenyl)acetic acid (378.0 mg, 0.001584 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (448.0 mg, 0.001178 mol) and N,N-diisopropylethylamine (600.0 μL, 0.003445 mol). The reaction mixture was stirred for 16 hours at 50° C. After most of the DMF was rotovaped, MeOH (20 mL) and 2N NaOH (5 mL) were added to the residue. The solution was stirred for 1 hour at room temperature. MeOH was rotovaped and EtOAc (100 mL) was added, and the resultant solution was then washed with water (2×100 mL), Sat. NaHCO3, H2O, and brine. The EtOAc layer was dried by MgSO4 and was rotovaped. The resultant solution was washed with DCM and then purified with silica-gel. The final product was obtained as a solid. MS m/z=455.1 (M+1). 1H NMR (400 MHz; DMSO-d6) δ 10.09(s, 1 H), 8.09(d, J=8.0 Hz, 1 H), 7.89(s, 1 H), 7.80(d, J=7.6 Hz, 1 H), 7.75-7.65(m, 2 H), 7.55-7.40(m, 2 H), 6.63(d, J=7.6 Hz, 1 H), 4.98-4.85(m, 3 H), 3.92(s, 2 H), 3.85-3.65 (m, 4 H).

Workup

  1. stirringThe solution was stirred for 1 hour at room temperature
  2. washthe resultant solution was then washed with water (2×100 mL), Sat. NaHCO3, H2O, and brine
  3. dry with materialThe EtOAc layer was dried by MgSO4
  4. washThe resultant solution was washed with DCM
  5. custompurified with silica-gel

Sources & evidence

ORD record
ord-0dba5fdb3c4f431dbdbf16a9e3c3287c
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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