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

HRID 279641

反応式

HRID 279641 の反応式
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

参加物

6

反応物 4

HCID 11776Triphenylphosphine2 回HCID 220568ethyl N-ethoxycarbonyliminocarbamate2 回HCID 5509251H-1,2,4-Triazole-1-ethanol2 回HCID 1356711794-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-a2176d288b9d4122bb74d7c0503ecf19
出典データセット
uspto-grants-2002_03
特許番号
US06362336B1

関連ノート

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