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

HRID 1366505Notes

Reaction equation

HRID 1366505 reaction equation
[F:1][C:2]1[C:3]([N:11]2[CH2:15][C:14]([CH3:17])([CH3:16])[CH:13]([N:18]([CH3:20])[CH3:19])[CH2:12]2)=[N:4][C:5]([CH3:10])=[N:6][C:7]=1[NH:8][NH2:9].[CH:21]1([CH2:26][C@H:27]([CH2:31][N:32]([CH:41]=[O:42])[O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:28](O)=[O:29])[CH2:25][CH2:24][CH2:23][CH2:22]1.CN1CCOCC1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl>CN(C=O)C>[CH:21]1([CH2:26][C@@H:27]([C:28]([NH:9][NH:8][C:7]2[C:2]([F:1])=[C:3]([N:11]3[CH2:12][CH:13]([N:18]([CH3:20])[CH3:19])[C:14]([CH3:17])([CH3:16])[CH2:15]3)[N:4]=[C:5]([CH3:10])[N:6]=2)=[O:29])[CH2:31][N:32]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:41]=[O:42])[CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 66936077racemic 1-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-N,N,4,4-tetramethyl-3-pyrrolidinamine

Product 1

HCID 86636965[(2R)-2-(cyclopentylmethyl)-3-(2-{6-[4-(dimethylamino)-3,3-dimethyl-1-pyrrolidinyl]-5-fluoro-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamideYield 65.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of racemic 1-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-N,N,4,4-tetramethyl-3-pyrrolidinamine (0.0617 g, 0.219 mmol) in DMF (3 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (0.0637 g, 0.209 mmol), N-methylmorpholine (0.120 mL, 1.091 mmol), 1-hydroxy-7-azabenzotriazole (34 mg, 0.250 mmol), and EDC (48 mg, 0.250 mmol). The solution was stirred overnight and then purified directly by Gilson RPLC to give [(2R)-2-(cyclopentylmethyl)-3-(2-{6-[4-(dimethylamino)-3,3-dimethyl-1-pyrrolidinyl]-5-fluoro-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide (0.0775 g, 65% yield, mixture of diastereomers) as a pale yellow oil. LCMS: (M+H)+: 570.3.

Workup

  1. custompurified directly by Gilson RPLC

Sources & evidence

ORD record
ord-a6c6213b0ebc46548de45797c96a47d9
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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