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

HRID 1908615笔记

反应方程式

HRID 1908615 反应方程式
[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]

参与物

9

反应物 4

HCID 6363异丙胺HCID 6422三氟乙酸HCID 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

产物 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

试剂、催化剂与溶剂 4

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 1140甲苯溶剂HCID 6228N,N-二甲基甲酰胺溶剂HCID 6344二氯甲烷溶剂

实验过程

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.

后处理

  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

来源与证据

ORD记录
ord-8bb234312abc489ca2b565ef7da2c7a3
来源数据集
uspto-grants-2013_12
专利号
US08598179B2

反应笔记

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