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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
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HRID 1267914 반응식
[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]
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참가 물질

4

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene
용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-b3ac5dd333934e41bf8bb9fc468dc7a2
출처 데이터셋
uspto-grants-2003_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06555541B1

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