Triphenylphosphine → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-t-butoxycarbonylamino)ethoxy)quinazoline

HRID 279588

反応式

HRID 279588 の反応式
[CH3:1][N:2]([CH2:10][CH2:11][OH:12])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25](O)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:12][CH2:11][CH2:10][N:2]([CH3:1])[C:3]([O:5][C:6]([CH3:9])([CH3:7])[CH3:8])=[O:4])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 545700N-(tert-Butoxycarbonyl)-N-methyl-2-aminoethanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 226250154-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-t-butoxycarbonylamino)ethoxy)quinazoline収率 188.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of 2-(N-methyl-N-t-butoxycarbonylamino)ethanol (116 mg, 0.7 mmol) in methylene chloride (1 ml) was added to a suspension of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (160 mg, 0.5 mmol), (prepared as described for the starting material in Example 24), and triphenylphosphine (393 mg, 1.5 mmol) in methylene chloride (5 ml). Diethyl azodicarboxylate (261 mg, 1.5 mmol) was then added dropwise and the mixture was stirred at ambient temperature for 4 hours. The reaction mixture was poured onto a column of silica and eluted with a gradient of methylene chloride/acetonitrile/methanol (70/30/0 to 70/20/10). The partially purified product was further purified by column chromatography eluting with a gradient of methylene chloride/ether/methanol (60/40/0 to 60/10/30). The pure oil was crystallised from ether, collected by filtration and washed with ether to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-t-butoxycarbonylamino)ethoxy)quinazoline (450 mg, 63%).

後処理

  1. custom(prepared
  2. additionThe reaction mixture was poured onto a column of silica
  3. washeluted with a gradient of methylene chloride/acetonitrile/methanol (70/30/0 to 70/20/10)
  4. customThe partially purified product was further purified by column chromatography
  5. washeluting with a gradient of methylene chloride/ether/methanol (60/40/0 to 60/10/30)
  6. customThe pure oil was crystallised from ether
  7. filtrationcollected by filtration
  8. washwashed with ether

出典と根拠

ORDレコード
ord-bbebecbcf0f5430baabff4b1a8c7b3ef
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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