[(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide → [(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl]hydroxyformamide

HRID 1366550Notes

Reaction equation

HRID 1366550 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][NH:9][C:10](=[O:30])[C@H:11]([CH2:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)[CH2:12][N:13]([O:16]CC2C=CC=CC=2)[CH:14]=[O:15])[C:5]([F:31])=[C:4]([N:32]2[CH2:37][CH:36]3[C:34]([N:38]([CH3:40])[CH3:39])([CH2:35]3)[CH2:33]2)[N:3]=1>CO.[OH-].[OH-].[Pd+2]>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][NH:9][C:10](=[O:30])[C@H:11]([CH2:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)[CH2:12][N:13]([OH:16])[CH:14]=[O:15])[C:5]([F:31])=[C:4]([N:32]2[CH2:37][CH:36]3[C:34]([N:38]([CH3:40])[CH3:39])([CH2:35]3)[CH2:33]2)[N:3]=1

Participants

4

Reactant 1

HCID 86636983[(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

Product 1

HCID 58000749[(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl]hydroxyformamideYield 49.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of [(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (assumed 0.6123 g, 1.067 mmol) in MeOH (10 mL) was added 20% Pd(OH)2/C (50% water, 61 mg). The mixture was hydrogenated for 6.5 h and then filtered. The filtrate was concentrated in vacuo and purified by Gilson RPLC to give [(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl]hydroxyformamide (0.2537 g, 49% yield for 2 steps, mixture of diastereomers) as a light pink solid. LCMS: (M+H)+: 484.2.

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated in vacuo
  3. custompurified by Gilson RPLC

Sources & evidence

ORD record
ord-883886b86e8d4f629aff49b6055c874e
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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