Tricyclohexylphosphine → (5-(4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl)-furan-2-ylmethyl)-carbamic acid tert-butyl ester

HRID 1725134ノート

反応式

HRID 1725134 の反応式
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26](I)[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+].[C:54]([O:58][C:59](=[O:67])[NH:60][CH2:61][C:62]1[O:63][CH:64]=[CH:65][CH:66]=1)([CH3:57])([CH3:56])[CH3:55]>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.[Pd](Cl)Cl>[C:54]([O:58][C:59](=[O:67])[NH:60][CH2:61][C:62]1[O:63][C:64]([C:26]2[CH:27]=[C:28]3[C:23](=[CH:24][CH:25]=2)[N:22]=[CH:21][N:20]=[C:19]3[NH:18][C:5]2[CH:6]=[CH:7][C:8]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=3)=[C:3]([Cl:2])[CH:4]=2)=[CH:65][CH:66]=1)([CH3:57])([CH3:55])[CH3:56]

参加物

9

反応物 4

HCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 4935496Tert-butyl (furan-2-ylmethyl)carbamateHCID 66623345[3-Chloro-4-(3-fluorobenzyloxy)phenyl](6-iodoquinazolin-4-yl)amine hydrochloride

生成物 1

HCID 66623782(5-(4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl)-furan-2-ylmethyl)-carbamic acid tert-butyl ester収率 46.4%

試薬・触媒・溶媒 4

HCID 24290Palladium Chloride触媒HCID 74236Tetrabutylammonium Bromide触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
110 °C

実験手順

[3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.913 g, 1.68 mmol) (from Step E, Example 1) is dissolved in DMF (20 ml) and the solution is degassed under nitrogen. The above solution is added over 10 hours to a heated (110° C.) degassed suspension of tricyclohexyl phosphine (0.475 g, 1.7 mmol), palladium dichloride (15.2 mg, 0.086 mmol), potassium acetate (0.35 g, 3.6 mmol), tetra n-butyl ammonium bromide (0.552 g, 2.15 mmol), and Furan-2-ylmethyl-carbamic acid tert-butyl ester (2.9 g, 15 mmol) in DMF (5 ml). Heating is continued for 9 hours after the end of addition. The reaction mixture is cooled, diluted with water and extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution yields 0.450 g (0.78 mmol, 46%) of the clean desired product.

後処理

  1. customthe solution is degassed under nitrogen
  2. additionThe above solution is added over 10 hours to
  3. customdegassed
  4. temperatureHeating
  5. additionafter the end of addition
  6. temperatureThe reaction mixture is cooled
  7. extractionextracted with EtOAc
  8. dry with materialThe combined organic extracts are dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. washFlash chromatography on silica with 10-50% EtOAc:hexanes gradient elution

出典と根拠

ORDレコード
ord-c3139e7cd356450faede16d21c8d1acb
出典データセット
uspto-grants-2009_02
特許番号
US07488823B2

反応ノート

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