1,2-Dichloroethane → [(2R)-3-(2-{2-chloro-5-fluoro-6-[(4S)-4-hydroxy-3,3-dimethyl-1-pyrrolidinyl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide

HRID 1366483Notes

Reaction equation

HRID 1366483 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][C:11]([CH3:14])([CH3:13])[C@H:10]([OH:15])[CH2:9]2)[C:5]([F:16])=[C:4]([NH:17][NH2:18])[N:3]=1.[CH:19]1([CH2:24][C@H:25]([CH2:29][N:30]([CH:38]=[O:39])[O:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)[C:26](O)=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]1.CN1CCOCC1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:17][NH:18][C:26](=[O:27])[C@H:25]([CH2:24][CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23]2)[CH2:29][N:30]([O:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)[CH:38]=[O:39])[C:5]([F:16])=[C:6]([N:8]2[CH2:9][C@@H:10]([OH:15])[C:11]([CH3:14])([CH3:13])[CH2:12]2)[N:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 57937086(2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acidHCID 86636957(3S)-1-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-4,4-dimethyl-3-pyrrolidinol

Product 1

HCID 86636956[(2R)-3-(2-{2-chloro-5-fluoro-6-[(4S)-4-hydroxy-3,3-dimethyl-1-pyrrolidinyl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamideYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S)-1-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-4,4-dimethyl-3-pyrrolidinol (0.131 g, 0.475 mmol) in DMF (3 mL) was added added (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (0.1181 g, 0.395 mmol), N-methylmorpholine (0.220 ml, 2.001 mmol), 1-hydroxy-7-azabenzotriazole (64 mg, 0.470 mmol), and EDC (91 mg, 0.475 mmol). The solution was stirred overnight and then purified directly by Gilson RPLC to afford [(2R)-3-(2-{2-chloro-5-fluoro-6-[(4S)-4-hydroxy-3,3-dimethyl-1-pyrrolidinyl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (0.1294 g, 59% yield) as an orange oil. LCMS: (M+H)+: 557.3.

Workup

  1. custompurified directly by Gilson RPLC

Sources & evidence

ORD record
ord-a0104f3308ad4f8d8ac4d9aeef022b0e
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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