Methanol → (R)-2-(4-Chloro-3-fluorophenyl)-N-(2-(1-hydroxypropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)acetamide

HRID 1161265Notes

Reaction equation

HRID 1161265 reaction equation
C([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[NH2:18])[C:9]1=[O:19])[CH3:7])(=O)C.C(Cl)Cl.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][C:31](O)=[O:32])=[CH:26][C:25]=1[F:34].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.CO.C(=O)([O-])[O-].[K+].[K+]>>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][C:31]([NH:18][C:14]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:15]=2[CH:16]=[CH:17][N:8]([C@H:6]([CH3:7])[CH2:5][OH:4])[C:9]3=[O:19])=[O:32])=[CH:26][C:25]=1[F:34]

Participants

8

Reactant 7

HCID 887MethanolHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 38149542-(4-Chloro-3-fluorophenyl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59515825(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)propyl acetate

Product 1

HCID 59515803(R)-2-(4-Chloro-3-fluorophenyl)-N-(2-(1-hydroxypropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)acetamide

Procedure

To a solution of (R)-2-(5-amino-1-oxoisoquinolin-2(1H)-yl)propyl acetate (800 mg, 0.003 mol) in methylene chloride (20 mL, 0.2 mol) was added 2-(4-chloro-3-fluorophenyl)acetic acid (870 mg, 0.0046 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (2900 mg, 0.0077 mol) and N,N-diisopropylethylamine (3000 μL, 0.02 mol). The reaction mixture was stirred overnight at room temperature and then concentrated. methanol (20 mL, 0.6 mol) and potassium carbonate (1000 mg, 0.009 mol) were added and the mixture was allowed to stir at room temperature for one hour. Volatiles were removed and the residue was taken up in methylene chloride (100 ml). The mixture was washed with aqueous NaHCO3 (150 ml), brine (150 ml) and water (200 ml). The layers were separated and the organics dried over Na2SO4 and concentrated under reduced pressure. The mixture was then purified by flash chromatography (Ethyl acetate: Hexanes, 0-40%). The combined pure fractions were reduced in vacuo to yield the title compound as a yellow solid. M+1=389.1

Workup

  1. concentrationconcentrated
  2. stirringto stir at room temperature for one hour
  3. customVolatiles were removed
  4. washThe mixture was washed with aqueous NaHCO3 (150 ml), brine (150 ml) and water (200 ml)
  5. customThe layers were separated
  6. dry with materialthe organics dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe mixture was then purified by flash chromatography (Ethyl acetate: Hexanes, 0-40%)

Sources & evidence

ORD record
ord-31be8bb9574d41878c4324fb21c78b6e
Source dataset
uspto-grants-2010_10
Patent number
US07816371B2

Reaction notes

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