Methanol → HCID 68523091, compound

HRID 1157472Notes

Reaction equation

HRID 1157472 reaction equation
[C:1]([NH:5][C:6]([CH2:8][N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH:20]=[CH:21][CH2:22][CH2:23]OS(C)(=O)=O)[CH:16]=2)[N:11]=[C:10]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.C([O-])([O-])=O.[K+].[K+].CO>C(#N)C.ClCCl>[NH4+:5].[OH-:7].[C:1]([NH:5][C:6](=[O:7])[CH2:8][N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH:20]=[CH:21][CH2:22][CH2:23][N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH:16]=2)[N:11]=[C:10]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 72311187HCID 72311187, compound

Product 2

HCID 14923Ammonium HydroxideHCID 68523091HCID 68523091, compoundYield 121.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of methanesulfonic acid 4-[3-(tert-butylcarbamoylmethyl)-2-(3-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-6-yl]but-3-enyl ester (528 mg, 1.02 mmol), pyrrolidine (260 μL, 3.06 mmol), and K2CO3 (705 mg, 5.10 mmol) in dry acetonitrile (5 mL) was heated at reflux temperature for 4 h. The mixture was partitioned between water (10 mL) and ethyl acetate (10 mL). The layers were separated, and the aqueous phase was extracted with ethyl acetate (10 mL). The combined organic layers were washed with brine (10 mL), dried (MgSO4) and concentrated in vacuo to give the crude product as red-brown foam. Chromatography on silica gel with methanol:dichloromethane:NH4OH (aq.) (2:37:1, v/v) as eluent afforded N-tert-butyl-2-[2-(3-chlorophenyl)-4-oxo-6-(4-pyrrolidin-1-ylbut-1-enyl)-4H-quinazolin-3-yl]acetamide (EXAMPLE 10a) (308 mg, 0.62 mmol, 61%) as a yellow foam.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 4 h
  3. customThe mixture was partitioned between water (10 mL) and ethyl acetate (10 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with ethyl acetate (10 mL)
  6. washThe combined organic layers were washed with brine (10 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give the crude product as red-brown foam

Sources & evidence

ORD record
ord-49bbce293ca543ca9ed2133b8bb884cc
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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