Pyrrolidine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-pyrrolidin-1-ylcarbonylpropoxy)quinazoline

HRID 547202Notes

Reaction equation

HRID 547202 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=3[F:32])=[N:19][CH:20]=[N:21]2)=[CH:16][C:15]=1[O:33][CH3:34])(O)=[O:8].[NH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1>C(Cl)Cl.CN(C=O)C.CN(C)C(=O)C>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:18]2[C:17]3[C:22](=[CH:23][C:14]([O:13][CH2:12][CH2:11][CH2:10][C:7]([N:35]4[CH2:39][CH2:38][CH2:37][CH2:36]4)=[O:8])=[C:15]([O:33][CH3:34])[CH:16]=3)[N:21]=[CH:20][N:19]=2)=[C:26]([F:32])[CH:27]=1

Participants

7

Reactant 3

HCID 31268PyrrolidineHCID 65578Oxalyl chlorideHCID 224782937-(3-Carboxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline

Product 1

HCID 187534424-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-pyrrolidin-1-ylcarbonylpropoxy)quinazolineYield 70.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

Oxalyl chloride (0.4 ml, 2.2 mmol) was added to a suspension of 7-(3-carboxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (260 mg, 0.64 mmol), (prepared as described for the starting material in Example 42), in methylene chloride (25 ml) followed by 1 drop of DMF. The mixture was stirred at ambient temperature for 2.5 hours and the volatiles were removed by evaporation. A solution of pyrrolidine (0.13 ml, 2.1 mmol) in N,N-dimethylacetamide (8 ml) was added to the solid residue and the mixture was stirred at ambient temperature for 2 hours. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (100/8/1). The purified product was triturated with acetone, collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-pyrrolidin-1-ylcarbonylpropoxy)quinazoline (206 mg, 70%).

Workup

  1. custom(prepared
  2. customthe volatiles were removed by evaporation
  3. stirringthe mixture was stirred at ambient temperature for 2 hours
  4. customThe volatiles were removed by evaporation
  5. customthe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol/aqueous ammonia (100/8/1)
  7. customThe purified product was triturated with acetone
  8. filtrationcollected by filtration
  9. customdried

Sources & evidence

ORD record
ord-d30d96e57fd94568989bb18159d1dc59
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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