((2R)-2-(Cyclopentylmethyl)-3-{2-[2-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-3-oxopropyl)[(phenylmethyl)oxy]formamide → ((2R)-2-(Cyclopentylmethyl)-3-{2-[2-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-3-oxopropyl)hydroxyformamide

HRID 1366422Notes

Reaction equation

HRID 1366422 reaction equation
[CH:1]1([CH2:6][C@@H:7]([C:20]([NH:22][NH:23][C:24]2[C:29]([F:30])=[C:28]([N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)[N:27]=[C:26]([CH2:38][CH3:39])[N:25]=2)=[O:21])[CH2:8][N:9]([O:12]CC2C=CC=CC=2)[CH:10]=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1>CO.[Pd]>[CH:1]1([CH2:6][C@@H:7]([C:20]([NH:22][NH:23][C:24]2[C:29]([F:30])=[C:28]([N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)[N:27]=[C:26]([CH2:38][CH3:39])[N:25]=2)=[O:21])[CH2:8][N:9]([OH:12])[CH:10]=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 1

HCID 86636931((2R)-2-(Cyclopentylmethyl)-3-{2-[2-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-3-oxopropyl)[(phenylmethyl)oxy]formamide

Product 1

HCID 58000605((2R)-2-(Cyclopentylmethyl)-3-{2-[2-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-3-oxopropyl)hydroxyformamideYield 70.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

A mixture of ((2R)-2-(cyclopentylmethyl)-3-{2-[2-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-3-oxopropyl)[(phenylmethyl)oxy]formamide (17.1 g, 31.61 mmol) and 10% Pd/C (4 g) suspended in MeOH (400 mL) was stirred under a balloon of H2 gas. After 2 h, and additional 2 g of fresh 10% Pd/C was added. The resulting suspension was stirred for another 1.5 h under a hydrogen atmosphere until the staring material was consumed. The Pd/C was removed by filtration through Celite, washing with MeOH and CH2Cl2. The filtrate was concentrated in vacuo. As the evaporation proceeded, the product crystallized out from the remaining solution. The evaporation continued until only ˜50 mL of liquid remained. The crystals were then collected by filtration to provide the product as a white solid (10.0 g). The filtrate was further evaporated to give a second crop of crystals (1.5 g) as the pure product. In the same way, a third crop was collected. The combined yield of ((2R)-2-(cyclopentylmethyl)-3-{2-[2-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-3-oxopropyl)hydroxyformamide was 86% (12.2 g). LCMS: (M+H)+: 452.1.

Workup

  1. stirringThe resulting suspension was stirred for another 1.5 h under a hydrogen atmosphere until the staring material
  2. customwas consumed
  3. customThe Pd/C was removed by filtration through Celite
  4. washwashing with MeOH and CH2Cl2
  5. concentrationThe filtrate was concentrated in vacuo
  6. customAs the evaporation
  7. customthe product crystallized out from the remaining solution
  8. customThe evaporation
  9. filtrationThe crystals were then collected by filtration

Sources & evidence

ORD record
ord-f078b156a021451dbaf5ef91b83af414
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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