[(2R)-3-(2-{2-chloro-6-[3-(dimethylamino)-2,2-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide → HCID 58000615, compound

HRID 1366536Notes

Reaction equation

HRID 1366536 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[CH2:36][CH2:35][CH:34]([N:37]([CH3:39])[CH3:38])[C:33]2([CH3:41])[CH3:40])[N:3]=1>CO.[Rh]>[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[CH2:36][CH2:35][CH:34]([N:37]([CH3:39])[CH3:38])[C:33]2([CH3:41])[CH3:40])[N:3]=1

Participants

4

Reactant 1

HCID 86636979[(2R)-3-(2-{2-chloro-6-[3-(dimethylamino)-2,2-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

Product 1

HCID 58000615HCID 58000615, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of [(2R)-3-(2-{2-chloro-6-[3-(dimethylamino)-2,2-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (0.1737 g, 0.294 mmol) in MeOH (10 mL) was added 5% Rh/C (175 mg). The mixture was hydrogenated at 50 psi overnight, and was then filtered through a 0.2 μM membrane and concentrated in vacuo. To a solution of the residue in MeOH (4 mL) was added 20% Pd(OH)2/C (50% water, 5 mg). The mixture was hydrogenated under balloon pressure for 50 min. The mixture was then filtered though a 0.2 μM membrane, and the solution was concentrated in vacuo. The residue was purified by Gilson RPLC to give [(2R)-3-(2-{2-chloro-6-[3-(dimethylamino)-2,2-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl]hydroxyformamide (0.0670 g, 46% yield, mixture of diastereomers) as a while solid following crystallization from EtOAc-hexanes. LCMS: (M+H)+: 500.3.

Workup

  1. customwas hydrogenated at 50 psi overnight
  2. filtrationwas then filtered through a 0.2 μM membrane
  3. concentrationconcentrated in vacuo
  4. additionTo a solution of the residue in MeOH (4 mL) was added 20% Pd(OH)2/C (50% water, 5 mg)
  5. filtrationThe mixture was then filtered though a 0.2 μM membrane
  6. concentrationthe solution was concentrated in vacuo
  7. customThe residue was purified by Gilson RPLC

Sources & evidence

ORD record
ord-f8e2dc6ad4834405ba1ebb6204bd72e4
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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