Hydrochloric Acid → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-(1,2,4-triazol-1-yl)propoxy)quinazoline hydrochloride

HRID 279645노트

반응식

HRID 279645 반응식
N(C(OCC)=O)=NC(OCC)=O.[OH:13][CH2:14][CH2:15][CH2:16][N:17]1[CH:21]=[N:20][CH:19]=[N:18]1.[Cl:22][C:23]1[CH:42]=[CH:41][C:26]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][C:34](O)=[C:35]([O:38][CH3:39])[CH:36]=3)[N:31]=[CH:30][N:29]=2)=[C:25]([F:43])[CH:24]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>C(Cl)Cl.C(Cl)Cl.CO>[ClH:22].[Cl:22][C:23]1[CH:42]=[CH:41][C:26]([NH:27][C:28]2[C:37]3[C:32](=[CH:33][C:34]([O:13][CH2:14][CH2:15][CH2:16][N:17]4[CH:21]=[N:20][CH:19]=[N:18]4)=[C:35]([O:38][CH3:39])[CH:36]=3)[N:31]=[CH:30][N:29]=2)=[C:25]([F:43])[CH:24]=1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 47118023-(1H-1,2,4-triazol-1-yl)propan-1-olHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

생성물 1

HCID 226249624-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-(1,2,4-triazol-1-yl)propoxy)quinazoline hydrochloride수율 83.9%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 21226129Dichloromethane methanol용매

실험 절차

Diethyl azodicarboxylate (295 μl, 1.8 mmol) was added dropwise to a solution of 1-(3-hydroxypropyl)-[1,2,4]-triazole (119 mg, 0.93 mmol), (EP0060696 A1), 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.62 mmol), (prepared as described for the starting material in Example 24), and triphenylphosphine (492 g, 1.8 mmol) in methylene chloride (4 ml) and the mixture stirred for 3 hours at ambient temperature. The mixture was purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (60/32/8). The purified product was triturated with a mixture of pentane and ether, collected by filtration and dried under vacuum to give a white solid. This solid was dissolved in methylene chloride/methanol and ethereal hydrogen chloride (1 ml of a 5M solution) was added. The volatiles were removed by evaporation. The solid residue was suspended in ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(1,2,4-triazol-1-yl)propoxy)quinazoline hydrochloride (121 mg, 39%).

후처리

  1. custom(prepared
  2. customThe mixture was purified by column chromatography
  3. washeluting with methylene chloride/acetonitrile/methanol (60/32/8)
  4. customThe purified product was triturated with a mixture of pentane and ether
  5. filtrationcollected by filtration
  6. customdried under vacuum
  7. customto give a white solid
  8. customThe volatiles were removed by evaporation
  9. filtrationcollected by filtration
  10. washwashed with ether
  11. customdried under vacuum

출처 및 근거

ORD 기록
ord-78d990494203498ea8a5602c422405a9
출처 데이터셋
uspto-grants-2002_03
특허 번호
US06362336B1

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