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Lawesson's reagent → 4-(3-{2-[Tert-butoxycarbonyl-(3,4-difluoro-phenyl)-amino]-thioacetylamino}-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1267914
ノート
印刷プレビュー

反応式

HRID 1267914 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([NH:22][C:23](=O)[CH2:24][N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=3)[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:51])=CC=1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([NH:22][C:23](=[S:51])[CH2:24][N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=3)[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
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

4

反応物 2

HCID 87949Lawesson's reagentHCID 120432244-(3-{2-[Tert-butoxycarbonyl-(3,4-difluoro-phenyl)-amino]-acetylamino}-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 542472024-(3-{2-[Tert-butoxycarbonyl-(3,4-difluoro-phenyl)-amino]-thioacetylamino}-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl ester収率 82.2%

試薬・触媒・溶媒 1

HCID 1140Toluene
溶媒

反応条件

温度
100 °C

実験手順

To a solution of 4-(3-{2-[tert-butoxycarbonyl-(3,4-difluoro-phenyl)-amino]-acetylamino}-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl ester (160 mg) in toluene (4 ml) was added Lawesson's reagent (100 mg) and the reaction heated at 100° C. for 2.5 hr. After cooling to room temperature, the solvent was removed in vacuo to afford a yellow powder. Purification by NPHPLC (0-5% MeOH in CH2Cl2) afforded 4-(3-{2-[tert-butoxycarbonyl-(3,4-difluoro-phenyl)-amino]-thioacetylamino}-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl ester (120 mg). This was taken up in CH2Cl2 (1 ml) and trifluoroacetic acid (0.63 ml) added. After 2 hr stirring the reaction was poured into aqueous K2CO3 and the organic layer was separated, washed with aqueous K2CO3 and brine, dried (Na2SO4) and concentrated to leave yellow crystals. They were purified further by reverse phase HPLC to afford the title compound (14 mg).

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed in vacuo
  3. customto afford a yellow powder
  4. customPurification by NPHPLC (0-5% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-b3ac5dd333934e41bf8bb9fc468dc7a2
出典データセット
uspto-grants-2003_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06555541B1

反応ノート

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