1,2-Dichloroethane → [(2R)-3-(2-{2-chloro-5-fluoro-6-[(1-methylethyl)amino]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

HRID 1366398Notes

Reaction equation

HRID 1366398 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]([NH:30][CH:31]([CH3:33])[CH3:32])[C:27]([F:34])=[C:26]([NH:35][NH2:36])[N:25]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[Cl:23][C:24]1[N:25]=[C:26]([NH:35][NH:36][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:34])=[C:28]([NH:30][CH:31]([CH3:33])[CH3:32])[N:29]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 866369222-chloro-5-fluoro-6-hydrazino-N-(1-methylethyl)-4-pyrimidinamine

Product 1

HCID 86636923[(2R)-3-(2-{2-chloro-5-fluoro-6-[(1-methylethyl)amino]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamideYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (268 mg, 0.88 mmol), 2-chloro-5-fluoro-6-hydrazino-N-(1-methylethyl)-4-pyrimidinamine (assumed 253 mg of free base, 0.97 mmol), EDC (186 mg, 0.97 mmol), HOAt (132 mg, 0.97 mmol), and NMM (0.64 mL, 5.82 mmol) in DMF was stirred at room temperature overnight. The reaction mixture was then purified via reverse phase HPLC to provide [(2R)-3-(2-{2-chloro-5-fluoro-6-[(1-methylethyl)amino]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (74 mg, 17%). LCMS: (M+H)+: 507.1.

Workup

  1. customThe reaction mixture was then purified via reverse phase HPLC

Sources & evidence

ORD record
ord-6fc7817935f0486693a6b4612dcee393
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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