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Acetic Acid → 1-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-2-fluoro-propane-1,3,dione

HRID 1433063
ノート
印刷プレビュー

反応式

HRID 1433063 の反応式
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:29])[CH2:20][C:21]([C:23]4[S:24][C:25]([Cl:28])=[CH:26][CH:27]=4)=[O:22])[CH:15]([CH2:30][CH2:31][CH3:32])[C:14]3=[O:33])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[H-].[Na+].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:46])(=O)=O)=CC=1.C(O)(=O)C>C1COCC1>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:29])[CH:20]([F:46])[C:21]([C:23]4[S:24][C:25]([Cl:28])=[CH:26][CH:27]=4)=[O:22])[CH:15]([CH2:30][CH2:31][CH3:32])[C:14]3=[O:33])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 588007N-FluorobenzenesulfonimideHCID 872365911-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-propane-1,3,dione

生成物 1

HCID 872364831-[4-(4-Aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-2-fluoro-propane-1,3,dione

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

Prepared by a procedure of Differding and Ofner. (Synlett 1991, 187.). A solution of 1-[4-(4-aminoquinazoline-7-ylmethyl)-3-oxo-2-propyl-piperazine-1-yl]-3-(5-chloro-thiophen-2-yl)-propane-1,3,dione (0.486 g, 1 mmol) in 40 ml of THF is added dropwise to an ice cold suspension of NaH (0.16 g of 60% NaH, 4 mmol) and 5 ml of THF. After the mixture had stirred one hour at 0° C., a solution of N-fluorobenzenesulfonimide (Aldrich) (0.378 g, 1.2 mmol) in 10 ml of THF is added dropwise. The reaction is stirred overnight at room temperature before quenching with glacial acetic acid (0.23 ml, 0.240 g, 4 mmol). The volatiles are evaporated in vacuo and the residue purified by flash column chromatography eluting with a gradient of 5% CH3OH/H2CCl2 to 10% CH3OH/H2CCl2 to provide the product as a white solid. The product could be recrystallized from THF/hexane. M.P. 194-6° C. MS (ion spray) m/z 504, (M+H).

後処理

  1. customPrepared by a procedure of Differding and Ofner
  2. stirringThe reaction is stirred overnight at room temperature
  3. customThe volatiles are evaporated in vacuo
  4. customthe residue purified by flash column chromatography
  5. washeluting with a gradient of 5% CH3OH/H2CCl2 to 10% CH3OH/H2CCl2

出典と根拠

ORDレコード
ord-a9e62563cb244b6cb3107b7a2730c622
出典データセット
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07612075B2

反応ノート

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