Dimethylformamide → HCID 22478210, compound

HRID 2182556Notes

Reaction equation

HRID 2182556 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:29]=[C:28]2[C:23]([C:24]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[F:38])=[N:25][CH:26]=[N:27]2)=[CH:22][C:21]=1OC)(O)=[O:14].[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.CN([CH:50]=[O:51])C>CN(C)C1C=CN=CC=1>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([NH:30][C:24]2[C:23]3[C:28](=[CH:29][C:20]([O:19][CH2:18][CH2:17][CH2:16][C:13]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)=[O:14])=[CH:21][CH:22]=3)[N:27]=[C:26]([O:51][CH3:50])[N:25]=2)=[C:32]([F:38])[CH:33]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 224782937-(3-Carboxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline

Product 1

HCID 22478210HCID 22478210, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

1-(3-Dimethylaminopropyl)3-ethylcarbodiimide hydrochloride (94 mg, 4.9 mmol) was added to a mixture of 7-(3-carboxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (164 mg, 0.4 mmol), morpholine (0.11 g; 1.26 mmol) and 4-dimethylaminopyridine (200 mg, 1.64 mmol) in DMF (5 ml). The reaction mixture was stirred at ambient temperature for 24 hours and the volatiles were removed by evaporation. Water was added to the residue and the aqueous mixture was extracted with methylene chloride (3×30 ml). The extracts were combined and the solvent removed by evaporation. The residue was triturated with ether and the precipitate was collected by filtration. The solid 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)-methoxy-7-(3-morpholinocarbonylpropoxy)quinazoline (88 mg, 46%).

Workup

  1. customthe volatiles were removed by evaporation
  2. additionWater was added to the residue
  3. extractionthe aqueous mixture was extracted with methylene chloride (3×30 ml)
  4. customthe solvent removed by evaporation
  5. customThe residue was triturated with ether
  6. filtrationthe precipitate was collected by filtration
  7. customThe solid was purified by column chromatography
  8. washeluting with methylene chloride/methanol/aqueous ammonia (100/8/1)
  9. customThe purified product was triturated with acetone
  10. filtrationcollected by filtration
  11. customdried

Sources & evidence

ORD record
ord-5ec7208b4e7e4042ac83e534282b825c
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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