三苯基膦 → 4-{(S)-4-Carboxy-2-[(5-cyclobutoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]butyryl}-piperazine-1-carboxylic acid ethyl ester

HRID 1908613笔记

反应方程式

HRID 1908613 反应方程式
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:38])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([OH:31])[N:28]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=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].[CH:39]1(O)[CH2:42][CH2:41][CH2:40]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:38])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH:39]3[CH2:42][CH2:41][CH2:40]3)[N:28]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=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

6

反应物 4

HCID 11776三苯基膦HCID 76218环丁醇HCID 220568偶氮二甲酸二乙酯HCID 178473388HCID 178473388，化合物

产物 1

HCID 441264054-{(S)-4-Carboxy-2-[(5-cyclobutoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]butyryl}-piperazine-1-carboxylic acid ethyl ester

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂

实验过程

To a solution of 50 mg of 4-{(S)-4-tert-Butoxycarbonyl-2-[(5-hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester and 8 mg of Cyclobutanol in 2 ml of THF, 37 mg of polymerbound triphenyl phosphine (Fluka, 3 mmol triphenylphosphine/g resin) and 20 mg of Diethyl azodicarboxylate was added and stirred for 16 h. Then, the reaction mixture was filtered and the solvents were removed under reduced pressure. The residue was dissolved in 1 ml of DCM and 0.2 ml TFA. After 4 h 10 ml of toluene was added and 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. Yield: 2 mg MS (ES+): m/e=528.

后处理

  1. filtrationThen, the reaction mixture was filtered
  2. customthe solvents were removed under reduced pressure
  3. dissolutionThe residue was dissolved in 1 ml of DCM
  4. additionAfter 4 h 10 ml of toluene was added
  5. customthe solvents were removed under reduced pressure
  6. customThe residue was purified by preparative HPLC (
  7. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  8. additionThe fractions containing the product
  9. customwere evaporated
  10. customto yield a white solid

来源与证据

ORD记录
ord-d9de045fbb2d4b668f5b1ce3b1c3287a
来源数据集
uspto-grants-2013_12
专利号
US08598179B2

反应笔记

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