Methyl iodide → HCID 66855133, compound

HRID 1970623Notes

Reaction equation

HRID 1970623 reaction equation
[CH:1]1([O:5][C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:51])[C@@H:15]([NH:21][C:22]([C:24]3[CH:28]=[C:27]([O:29][CH2:30][C:31]([N:33]4[CH2:37][CH2:36][CH2:35][C@H:34]4[C:38](=[O:44])[NH:39][CH:40]4[CH2:43][CH2:42][CH2:41]4)=[O:32])[N:26]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[N:25]=3)=[O:23])[CH2:16][CH2:17][CH2:18][CH2:19][OH:20])[CH2:10][CH2:9]2)=[O:7])[CH2:4][CH2:3][CH2:2]1.I[CH3:53].[H-].[Na+]>C1COCC1>[CH:1]1([O:5][C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:51])[C@@H:15]([NH:21][C:22]([C:24]3[CH:28]=[C:27]([O:29][CH2:30][C:31]([N:33]4[CH2:37][CH2:36][CH2:35][C@H:34]4[C:38](=[O:44])[N:39]([CH:40]4[CH2:43][CH2:42][CH2:41]4)[CH3:53])=[O:32])[N:26]([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[N:25]=3)=[O:23])[CH2:16][CH2:17][CH2:18][CH2:19][OH:20])[CH2:10][CH2:9]2)=[O:7])[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 668550244-{(S)-2-[(5-{2-[(S)-2-(Cyclobutylcarbamoyl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-6-hydroxy-hexanoyl}-piperazine-1-carboxylic acid cyclobutyl ester

Product 1

HCID 66855133HCID 66855133, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 65 mg 4-{(S)-2-[(5-{2-[(S)-2-(Cyclobutylcarbamoyl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-6-hydroxy-hexanoyl}-piperazine-1-carboxylic acid cyclobutyl ester in 5 ml THF were added at −20° C. 6 l iodomethane and 5 mg sodium hydride (95%). After 2 h and 12 h equivalent amounts of iodomethane and sodium hydride were added before the reaction mixture was quenched with 0.1 M HCl and extracted with dichloromethane. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) to give the title compound as a mixture with its trifluoroacetyl ester. Repeated lyophilization from MeCN/water yielded the pure title compound. Yield: 17 mg MS (ES+): m/e=722.

Workup

  1. customwas quenched with 0.1 M HCl
  2. extractionextracted with dichloromethane
  3. customThe crude product obtained
  4. customafter evaporation of the solvent
  5. customwas purified by preparative HPLC (
  6. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-4030b577e5394e019a27e7f8d2f1bdb4
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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