Dichloromethane → N-(4-chloro-2-fluorophenyl)-6-methoxy-7-{[(3R)-1-methylpiperidin-3-yl]methoxy}quinazolin-4-amine

HRID 2182539

반응식

HRID 2182539 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([CH2:8][OH:9])[CH2:3]1.Cl[N:11]([C:19]1[C:28]2[C:23](=[CH:24][C:25](O)=[C:26]([O:29][CH3:30])[CH:27]=2)[N:22]=[CH:21][N:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C(Cl)[Cl:64]>>[Cl:64][C:15]1[CH:16]=[CH:17][C:12]([NH:11][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:9][CH2:8][C@@H:4]4[CH2:5][CH2:6][CH2:7][N:2]([CH3:1])[CH2:3]4)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:13]([F:18])[CH:14]=1

참가 물질

6

반응물 5

HCID 6344Dichloromethane2회HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 920113(R)-(1-methylpiperidin-3-yl)methanolHCID 1359906824-(Chloro-2-fluoroanilino)7-hydroxy-6-methoxyquinazoline

생성물 1

HCID 5329055N-(4-chloro-2-fluorophenyl)-6-methoxy-7-{[(3R)-1-methylpiperidin-3-yl]methoxy}quinazolin-4-amine수율 52%

실험 절차

A solution of (R)(1-methylpiperidin-3-yl)methanol (2.29 g, 18 mmol) in methylene chloride (10 ml) was added to a stirred mixture of 4-(chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (4.0 g, 12.5 mmol), (prepared as described for the starting material in Example 2), and triphenylphosphine (9.81 g, 37.5 mmol) in methylene chloride (200 ml). Diethyl azodicarboxylate (5.87 ml, 37 mmol) was added dropwise and the reaction mixture was stirred for 18 hours at ambient temperature. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (a gradient from 100/0/0 to 85/15/0.1). The purified product was triturated with ethyl acetate, collected by filtration, washed with ethyl acetate and dried to give (R)4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-3yl)methoxyquinazoline (2.78 g, 52%).

후처리

  1. custom(prepared
  2. customThe volatiles were removed by evaporation
  3. customthe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol/aqueous ammonia (a gradient from 100/0/0 to 85/15/0.1)
  5. customThe purified product was triturated with ethyl acetate
  6. filtrationcollected by filtration
  7. washwashed with ethyl acetate
  8. customdried

출처 및 근거

ORD 기록
ord-afcc66f358fc4275848cd8edfd980bed
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06897210B2

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