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

HRID 547181

反応式

HRID 547181 の反応式
[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

参加物

6

反応物 5

HCID 6344Dichloromethane2 回HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 920113(R)-(1-methylpiperidin-3-yl)methanolHCID 1359906824-(Chloro-2-fluoroanilino)7-hydroxy-6-methoxyquinazoline

生成物 1

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

実験手順

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-3-yl)methoxyquinazoline (2.78 g, 52%).

後処理

  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

出典と根拠

ORDレコード
ord-d739eec13d50423785ffdf18ba6ec4a6
出典データセット
uspto-grants-2011_05
特許番号
USRE042353E1

関連ノート

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