Triphenylphosphine → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(2-(1,2,4-triazol-1-yl)ethoxy)quinazoline hydrochloride

HRID 279641

반응식

HRID 279641 반응식
N(C(OCC)=O)=NC(OCC)=O.[ClH:13].[F:14][C:15]1[CH:34]=[C:33]([CH3:35])[C:32]([O:36]C(OC)=O)=[CH:31][C:16]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24](O)=[C:25](OC)[CH:26]=2)[N:21]=[CH:20][N:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:60]1([CH2:65][CH2:66][OH:67])[CH:64]=[N:63][CH:62]=[N:61]1>C(Cl)Cl>[ClH:13].[F:14][C:15]1[CH:34]=[C:33]([CH3:35])[C:32]([OH:36])=[CH:31][C:16]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:67][CH2:66][CH2:65][N:60]3[CH:64]=[N:63][CH:62]=[N:61]3)=[CH:25][CH:26]=2)[N:21]=[CH:20][N:19]=1

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 220568ethyl N-ethoxycarbonyliminocarbamate2회HCID 5509251H-1,2,4-Triazole-1-ethanol2회HCID 1356711794-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

생성물 1

HCID 226250324-(2-Fluoro-5-hydroxy-4-methylanilino)-7-(2-(1,2,4-triazol-1-yl)ethoxy)quinazoline hydrochloride수율 61.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Diethyl azodicarboxylate (244 mg, 1.4 mmol) was added dropwise to a suspension of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (261 mg, 0.7 mmol), (prepared as described for the starting material in Example 22), triphenylphosphine (367 mg, 1.4 mmol) and 2-(1,2,4-triazol-1-yl)ethanol (95 mg, 0.84 mmol), (Ann. Pharm. Fr. 1977, 35, 503-508), in methylene chloride (5 ml). The mixture was stirred for 1 hour at ambient temperature and further triphenylphosphine (184 mg, 0.7 mmol), 2-(1,2,4-triazol-1-yl)ethanol (63 mg, 0.56 mmol) and diethyl azodicarboxylate (122 mg, 0.7 mmol) were added. The mixture was stirred for a further 2.5 hours and the solvent was removed by evaporation. The residue was dissolved in methanol (5 ml) and 2M aqueous sodium hydroxide solution (2 ml) was added. The mixture was stirred for 20 minutes and the mixture was partitioned between ether and water. The aqueous layer was acidified to pH7 with 2M hydrochloric acid and the resulting precipitate was collected by filtration, washed with water, and dried under vacuum. The resulting solid was dissolved in methylene chloride/methanol and a 5M solution of hydrogen chloride in isopropanol (0.5 ml) was added. The volatiles were removed by evaporation, the solid was resuspended in ether, collected by filtration, washed with ether and dried under vacuum to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(2-(1,2,4-triazol-1-yl)ethoxy)quinazoline hydrochloride (180 mg, 56%).

후처리

  1. custom(prepared
  2. stirringThe mixture was stirred for a further 2.5 hours
  3. customthe solvent was removed by evaporation
  4. dissolutionThe residue was dissolved in methanol (5 ml)
  5. addition2M aqueous sodium hydroxide solution (2 ml) was added
  6. stirringThe mixture was stirred for 20 minutes
  7. customthe mixture was partitioned between ether and water
  8. filtrationthe resulting precipitate was collected by filtration
  9. washwashed with water
  10. customdried under vacuum
  11. dissolutionThe resulting solid was dissolved in methylene chloride/methanol
  12. additiona 5M solution of hydrogen chloride in isopropanol (0.5 ml) was added
  13. customThe volatiles were removed by evaporation
  14. filtrationcollected by filtration
  15. washwashed with ether
  16. customdried under vacuum

출처 및 근거

ORD 기록
ord-a2176d288b9d4122bb74d7c0503ecf19
출처 데이터셋
uspto-grants-2002_03
특허 번호
US06362336B1

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