Sodium Hydroxide → 7-((2-Chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxyquinazoline hydrochloride

HRID 1384583Notes

Reaction equation

HRID 1384583 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([CH2:10][O:11][C:12]2[CH:21]=[C:20]3[C:15]([C:16]([NH:22][C:23]4[CH:28]=[C:27]([O:29]C(OC)=O)[C:26]([CH3:34])=[CH:25][C:24]=4[F:35])=[N:17][CH:18]=[N:19]3)=[CH:14][C:13]=2[O:36][CH3:37])[CH:7]=[C:6]([CH3:38])[N:5]=1>CO>[ClH:3].[Cl:3][C:4]1[CH:9]=[C:8]([CH2:10][O:11][C:12]2[CH:21]=[C:20]3[C:15]([C:16]([NH:22][C:23]4[CH:28]=[C:27]([OH:29])[C:26]([CH3:34])=[CH:25][C:24]=4[F:35])=[N:17][CH:18]=[N:19]3)=[CH:14][C:13]=2[O:36][CH3:37])[CH:7]=[C:6]([CH3:38])[N:5]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 226249947-((2-Chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxyquinazoline

Product 1

HCID 226249337-((2-Chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxyquinazoline hydrochlorideYield 158.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
5 °C

Procedure

2M Aqueous sodium hydroxide solution (700 μl, 1.4 mmol) was added to a suspension of 7-((2-chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxyquinazoline (360 mg, 0.7 mmol) in methanol (10 ml) cooled at 5° C. and the mixture was then stirred for 30 minutes at ambient temperature. The solvent was removed by evaporation, the residue diluted with water (10 ml) and the mixture adjusted to pH7 with 1M hydrochloric acid. The resulting solid was collected by filtration, washed with water and ether, and dried under vacuum. This solid was dissolved in methanol (5 ml) and a 7M solution of hydrogen chloride in methanol (3 ml) was added. The precipitate was collected by filtration, washed with methanol and dried under vacuum to give 7-((2-chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxyquinazoline hydrochloride (273 mg, 74%). 1H NMR Spectrum: (DMSOd6; CF3COOD) 2.18(s, 3H); 2.50(s, 3H); 4.04(s, 3H); 5.42(s, 2H) 6.9(d, 1H); 7.12(d, 1H); 7.35(s, 1H); 7.38(s, 1H); 7.42(s, 1H); 8.21(s, 1H); 8.81(s, 1H) MS-ESI: 455 [MH]+

Workup

  1. customThe solvent was removed by evaporation
  2. additionthe residue diluted with water (10 ml)
  3. filtrationThe resulting solid was collected by filtration
  4. washwashed with water and ether
  5. customdried under vacuum
  6. dissolutionThis solid was dissolved in methanol (5 ml)
  7. additiona 7M solution of hydrogen chloride in methanol (3 ml) was added
  8. filtrationThe precipitate was collected by filtration
  9. washwashed with methanol
  10. customdried under vacuum

Sources & evidence

ORD record
ord-611f800d6d31456fa54941f696728a62
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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