Water → (S)-2-amino-4-((1-(4-oxo-3-phenyl-5-(pyridazin-4-yl)-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 518247ノート

反応式

HRID 518247 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:19](=[O:27])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3Cl)[N:12]=2)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:36]1[CH:41]=[CH:40][N:39]=[N:38][CH:37]=1)CCC.O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:19](=[O:27])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[C:36]3[CH:41]=[CH:40][N:39]=[N:38][CH:37]=3)[N:12]=2)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 962WaterHCID 64097334-(Tributylstannyl)pyridazineHCID 71269828(S)-2-amino-4-((1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile

生成物 1

HCID 71269930(S)-2-amino-4-((1-(4-oxo-3-phenyl-5-(pyridazin-4-yl)-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of (S)-2-amino-4-(1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethylamino)pyrimidine-5-carbonitrile 59 (50 mg, 0.12 mmol), 4-(tributylstannyl)pyridazine (89 mg, 0.24 mmol) and PdCl2(dppf) (9.7 mg, 0.012 mmol) in 1,4-dioxane (5 mL) was stirred at reflux under argon for 16 h. The mixture was allowed to cool to RT, poured into water (20 mL) and extracted with ethyl acetate (2×15 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluting with 3% MeOH-DCM to afford the product, (S)-2-amino-4-((1-(4-oxo-3-phenyl-5-(pyridazin-4-yl)-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile 66. ESI-MS m/z: 462.2 [M+H]+.

後処理

  1. temperatureat reflux under argon for 16 h
  2. extractionextracted with ethyl acetate (2×15 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel eluting with 3% MeOH-DCM

出典と根拠

ORDレコード
ord-87d263f570084dc0a627a36483e6f52d
出典データセット
uspto-grants-2015_08
特許番号
US09115141B2

反応ノート

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