Triphenylphosphine → 4-Chloro-7-methoxy-6-[(1-methylpyrrolidin-3-yl)oxy]quinazoline

HRID 640018Notes

Reaction equation

HRID 640018 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:25][CH3:26])=[C:21]([OH:24])[CH:22]=2)[N:17]=[CH:16][N:15]=1.[CH3:27][N:28]1[CH2:32][CH2:31][CH:30](O)[CH2:29]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl.CO.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:25][CH3:26])=[C:21]([O:24][CH:30]3[CH2:31][CH2:32][N:28]([CH3:27])[CH2:29]3)[CH:22]=2)[N:17]=[CH:16][N:15]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 930741-Methyl-3-pyrrolidinolHCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 231324754-Chloro-7-methoxyquinazolin-6-ol

Product 1

HCID 866093914-Chloro-7-methoxy-6-[(1-methylpyrrolidin-3-yl)oxy]quinazolineYield 29.6%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

Diethyl azodicarboxylate (793 mg, 4.56 mmol) was added portionwise at room temperature to a stirred suspension of 4-chloro-7-methoxyquinazolin-6-ol (800 mg, 3.80 mmol), 1-methylpyrrolidin-3-ol (422 mg, 4.18 mmol) and triphenylphosphine (1.3 g, 4.96 mmol) in dichloromethane (16 ml). The reaction mixture was stirred for 1 hour and then a further portion of diethyl azodicarboxylate (360 ul) and triphenylphosphine (0.65 mg) were added. The mixture was stirred for 1 hour and the resulting orange solution was purified directly by silica gel chromatography eluting with a 0-10% mixture of methanol in dichloromethane to 4-chloro-7-methoxy-6-[(1-methylpyrrolidin-3-yl)oxy]quinazoline (330 mg, 28% yield) as a tan coloured solid:

Workup

  1. stirringThe mixture was stirred for 1 hour
  2. customthe resulting orange solution was purified directly by silica gel chromatography

Sources & evidence

ORD record
ord-56ccd2ff96864494bc9f73900838ecbb
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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