3-(Methylthio)propylamine → methyl (3R*,5S*)-5-[[(2-tert-butyl-4-{[3-(methylthio)propyl]amino}pyrimidin-5-yl)carbonyl](isobutyl)amino]piperidine-3-carboxylate

HRID 2192788노트

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HRID 2192788 반응식
[C:1]([C:5]1[N:10]=[C:9](Cl)[C:8]([C:12]([N:14]([CH2:32][CH:33]([CH3:35])[CH3:34])[C@@H:15]2[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C@H:17]([C:28]([O:30][CH3:31])=[O:29])[CH2:16]2)=[O:13])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:45][S:46][CH2:47][CH2:48][CH2:49][NH2:50].C(=O)([O-])O.[Na+]>CN(C=O)C>[C:1]([C:5]1[N:10]=[C:9]([NH:50][CH2:49][CH2:48][CH2:47][S:46][CH3:45])[C:8]([C:12]([N:14]([CH2:32][CH:33]([CH3:34])[CH3:35])[C@@H:15]2[CH2:20][NH:19][CH2:18][C@H:17]([C:28]([O:30][CH3:31])=[O:29])[CH2:16]2)=[O:13])=[CH:7][N:6]=1)([CH3:2])([CH3:3])[CH3:4]

참가 물질

6

반응물 4

HCID 777433-(Methylthio)propylamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 593565701-tert-butyl 3-methyl (3R*,5S*)-5-{[(2-tert-butyl-4-chloropyrimidin-5-yl)carbonyl](isobutyl)amino}piperidine-1,3-dicarboxylate

생성물 1

HCID 59625655methyl (3R*,5S*)-5-[[(2-tert-butyl-4-{[3-(methylthio)propyl]amino}pyrimidin-5-yl)carbonyl](isobutyl)amino]piperidine-3-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
80 °C

실험 절차

To a solution of 1-tert-butyl 3-methyl (3R*,5S*)-5-{[(2-tert-butyl-4-chloropyrimidin-5-yl)carbonyl](isobutyl)amino}piperidine-1,3-dicarboxylate (51.1% mg) and diisopropylethylamine (38 mg) in DMF (0.5 ml) was added a solution of 3-methylthiopropylamine (21 mg) in DMF (0.5 ml), and the mixture was stirred at 80° C. overnight. To the reaction mixture was added 2% aqueous sodium hydrogen carbonate and the mixture was extracted with ethyl acetate, and the extract was concentrated by a nitrogen gas blower. The residue was purified by reversed-phase preparative HPLC, and the object fraction was concentrated by a nitrogen gas blower. The residue was dissolved in trifluoroacetic acid/acetonitrile solution (20% (V/V), 1.0 ml), and the mixture was stirred at room temperature for 6 hr. The reaction mixture was concentrated by a nitrogen gas blower. The residue was neutralized with triethylamine (1 ml), saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The extract was concentrated by a nitrogen gas blower. The residue was purified by reversed-phase preparative HPLC, and the object fraction was concentrated by a nitrogen gas blower to give the object compound (6.4 mg).

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. concentrationthe extract was concentrated by a nitrogen gas blower
  3. customThe residue was purified by reversed-phase preparative HPLC
  4. concentrationthe object fraction was concentrated by a nitrogen gas blower
  5. dissolutionThe residue was dissolved in trifluoroacetic acid/acetonitrile solution (20% (V/V), 1.0 ml)
  6. stirringthe mixture was stirred at room temperature for 6 hr
  7. concentrationThe reaction mixture was concentrated by a nitrogen gas blower
  8. additionwas added
  9. extractionthe mixture was extracted with ethyl acetate
  10. concentrationThe extract was concentrated by a nitrogen gas blower
  11. customThe residue was purified by reversed-phase preparative HPLC
  12. concentrationthe object fraction was concentrated by a nitrogen gas blower

출처 및 근거

ORD 기록
ord-c77cd9236cd841ebbed48e6ed42d7f9c
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329691B2

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