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Triphenylphosphine → 4-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazoline

HRID 1384591
ノート
印刷プレビュー

反応式

HRID 1384591 の反応式
N(C(OCC)=O)=NC(OCC)=O.[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]([OH:31])=[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.[CH3:54][C:55]1[CH:60]=[C:59]([N:61]([CH2:63][CH2:64]O)[CH3:62])[CH:58]=[C:57]([CH3:66])[N:56]=1.[O-2].[Al+3].[O-2].[O-2].[Al+3]>C(Cl)Cl.CO>[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:31][CH2:64][CH2:63][N:61]([C:59]4[CH:58]=[C:57]([CH3:66])[N:56]=[C:55]([CH3:54])[CH:60]=4)[CH3:62])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 9989226AluminaHCID 226250732-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 22624991
4-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazoline
収率 70.5%

試薬・触媒・溶媒 2

HCID 887Methanol触媒HCID 6344Dichloromethane溶媒

実験手順

Diethyl azodicarboxylate (261 mg, 1.5 mmol) was added dropwise 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), triphenylphosphine (393 mg, 1.5 mmol) and 2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethanol (125 mg, 0.7 mmol) in methylene chloride (5 ml) and the mixture stirred for 2 hours at ambient temperature. Methanol (10 drops) was added and the mixture was poured on to a column of neutral aluminium oxide and the product was separated by elution with methylene chloride/acetonitrile/methanol (60/35/35). The purified solid product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol and a solution of 3M ethereal hydrogen chloride (1 ml) was added. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(2-(N-(2,6-dimethyl-4-pyridyl)-N-methylamino)ethoxy)-6-methoxyquinazoline (170 mg, 61%). m.p. 208-212° C. 1H NMR Spectrum: (DMSOd6; CF3COOD) 2.52(s, 6H); 3.26(s, 3H); 3.98(s, 3H); 4.12(t, 2H); 4.46(t, 2H); 6.8(br s, 1H); 7.1(br s, 1H); 7.38(s, 1H); 7.46(dd, 1H); 7.62(t, 1H); 7.67(dd, 1H); 8.18(s, 1H); 8.89(s, 1H) MS-ESI: 482 [MH]+

後処理

  1. custom(prepared
  2. customthe product was separated by elution with methylene chloride/acetonitrile/methanol (60/35/35)
  3. customThe purified solid product was triturated with ether
  4. filtrationcollected by filtration
  5. dissolutionThe solid was dissolved in methylene chloride/methanol
  6. additiona solution of 3M ethereal hydrogen chloride (1 ml) was added
  7. filtrationThe solid was collected by filtration
  8. washwashed with ether
  9. customdried under vacuum

出典と根拠

ORDレコード
ord-06b84be3ce074ed9a1f66356d329df6f
出典データセット
uspto-grants-2001_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06258951B1

反応ノート

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