1,2-Dichloroethane → [(2r)-3-{2-[2-Chloro-5-fluoro-6-(3-hydroxy-3-methyl-1-pyrrolidinyl)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

HRID 1366523Notes

Reaction equation

HRID 1366523 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:23][C:24]1[N:29]=[C:28]([N:30]2[CH2:34][CH2:33][C:32]([CH3:36])([OH:35])[CH2:31]2)[C:27]([F:37])=[C:26]([NH:38][NH2:39])[N:25]=1.CN1CCOCC1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Cl:23][C:24]1[N:25]=[C:26]([NH:38][NH:39][C:8](=[O:10])[C@H:7]([CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH2:11][N:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[O:22])[C:27]([F:37])=[C:28]([N:30]2[CH2:34][CH2:33][C:32]([OH:35])([CH3:36])[CH2:31]2)[N:29]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 866369751-(2-Chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-3-methyl-3-pyrrolidinol

Product 1

HCID 87210047[(2r)-3-{2-[2-Chloro-5-fluoro-6-(3-hydroxy-3-methyl-1-pyrrolidinyl)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R)-3-Cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (0.122 g, 0.4 mmol), racemic 1-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-3-methyl-3-pyrrolidinol (0.104 g, 0.4 mmol), NMM (0.13 mL, 1.2 mmol), HOAt (0.054 g, 0.4 mmol), EDC (0.077 g, 0.4 mmol) and DMF (2 mL) were combined. When the reaction was complete, the mixture was purified by RP-HPLC to provide [(2R)-3-{2-[2-chloro-5-fluoro-6-(3-hydroxy-3-methyl-1-pyrrolidinyl)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide as a mixture of diastereomers (0.035 g, 16%). LCMS: (M+H)+=549.5.

Workup

  1. customthe mixture was purified by RP-HPLC

Sources & evidence

ORD record
ord-fa0cf73235e5476ca808ccd7910ac332
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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