Isopropylamine → 4-((S)-4-Carboxy-2-{[5-(1-isopropylcarbamoyl-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester

HRID 1908615노트

반응식

HRID 1908615 반응식
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:45])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][C:32]3([C:36](O)=[O:37])[CH2:35][CH2:34][CH2:33]3)[N:28]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18]C(C)(C)C)=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[B-](F)(F)(F)F.CCO[C:54]([C:56]([C:66]#N)=[N:57]OC(N(C)C)=[N+](C)C)=O.C(N)(C)C.C(O)(C(F)(F)F)=O>CN(C=O)C.O.C(Cl)Cl.C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:45])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][C:32]3([C:36](=[O:37])[NH:57][CH:56]([CH3:66])[CH3:54])[CH2:35][CH2:34][CH2:33]3)[N:28]([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([OH:18])=[O:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

참가 물질

9

반응물 4

HCID 6363IsopropylamineHCID 6422Trifluoroacetic acidHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669200494-((S)-4-tert-Butoxycarbonyl-2-{[5-(1-carboxy-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester

생성물 1

HCID 669202074-((S)-4-Carboxy-2-{[5-(1-isopropylcarbamoyl-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester

시약·촉매·용매 4

HCID 962Water용매HCID 1140Toluene용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 50 mg of 4-((S)-4-tert-Butoxycarbonyl-2-{[5-(1-carboxy-cyclobutoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid ethyl ester in 0.3 ml of DMF, 28 mg of TOTU, 36 mg of NEM and 10 mg of isopropylamine was added. The reaction mixture was allowed to stir at RT for 16 h. Then, the reaction mixture was diluted with water and filtered through a Chem Elut® cartridge by eluting with ethyl acetate. The solvents were removed under reduced pressure. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. This residue was dissolved in 1 ml of DCM, 0.2 ml of TFA was added at RT. After 4 h 20 ml of toluene was added and the solvents were removed under reduced pressure. The residue was dissolved in 3 ml of water and lyophilized to yield a white solid.

후처리

  1. filtrationfiltered through a Chem Elut® cartridge
  2. washby eluting with ethyl acetate
  3. customThe solvents were removed under reduced pressure
  4. customThe residue was purified by preparative HPLC (
  5. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  6. additionThe fractions containing the product
  7. customwere evaporated
  8. customto yield a white solid
  9. customthe solvents were removed under reduced pressure
  10. dissolutionThe residue was dissolved in 3 ml of water
  11. customto yield a white solid

출처 및 근거

ORD 기록
ord-8bb234312abc489ca2b565ef7da2c7a3
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598179B2

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