Water → 2-[3-(3-chlorophenyl)-7-((S)-2-methyl-3-pyrrolidin-1-ylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide

HRID 602283Notes

Reaction equation

HRID 602283 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH2:29][C:30](=[O:35])[NH:31][CH:32]([CH3:34])[CH3:33])[C:10](=[O:28])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([O:18][CH2:19][C@@H:20]([CH3:27])[CH2:21]OS(C)(=O)=O)[CH:12]=3)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[NH:42]1[CH2:46][CH2:45][CH2:44][CH2:43]1.O>C(#N)C.C(Cl)Cl>[NH4+:9].[OH-:18].[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH2:29][C:30]([NH:31][CH:32]([CH3:34])[CH3:33])=[O:35])[C:10](=[O:28])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([O:18][CH2:19][C@@H:20]([CH3:27])[CH2:21][N:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)[CH:12]=3)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 59684267HCID 59684267, compound

Product 2

HCID 14923Ammonium HydroxideHCID 247529002-[3-(3-chlorophenyl)-7-((S)-2-methyl-3-pyrrolidin-1-ylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamideYield 98.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of methanesulfonic acid (R)-3-[3-(3-chlorophenyl)-2-(isopropylcarbamoylmethyl)-1-oxo-1,2-dihydroisoquinolin-7-yloxy]-2-methylpropyl ester (310 mg, 0.595 mmol) in dry acetonitrile (3 mL) was added K2CO3 (412 mg, 2.98 mmol) and pyrrolidine (150 mL, 1.78 mmol). The mixture was heated at reflux temperature for 6 h and water (10 mL) was added. The resultant suspension was extracted with ethyl acetate (3×25 mL), and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification by chromatography on silica gel with MeOH:DCM:NH4OH (aq.) (1:18.9:0.1 v/v) gave 2-[3-(3-chlorophenyl)-7-((S)-2-methyl-3-pyrrolidin-1-ylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide (EXAMPLE 1) (146 mg, 0.294 mmol, 67%). Data for 2-[3-(3-chlorophenyl)-7-((S)-2-methyl-3-pyrrolidin-1-ylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide (EXAMPLE 1): 1H NMR (300 MHz, CDCl3): δ 7.83 (d, 1H), 7.47-7.37 (m, 5H), 7.30 (dd, 1H), 6.46 (s, 1H), 5.91 (br d, 1H), 4.45 (s, 2H), 4.15 (dd, 1H), 4.07 (septet, 1H), 3.91 (dd, 1H), 2.62-2.46 (br m, 5H), 2.36 (dd, 1H), 2.21 (dd, 1H), 1.80-1.76 (br m, 4H), 1.16 (d, 6H), 1.11 (d, 3H) ppm; MS (ESI) m/z: 496 ([M+H]+), 991 ([2M+H]+), 1013 ([2M+Na]+).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux temperature for 6 h
  3. extractionThe resultant suspension was extracted with ethyl acetate (3×25 mL)
  4. dry with materialthe combined organic extracts were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography on silica gel with MeOH

Sources & evidence

ORD record
ord-31f98f6ba6f54290bdf5f0b36e0b0852
Source dataset
uspto-grants-2011_03
Patent number
US07906504B2

Reaction notes

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