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

HRID 1366543Notes

Reaction equation

HRID 1366543 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[NH:25][C:26]([NH:33][CH2:34][C:35]([CH3:43])([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[CH3:36])=[C:27]([F:32])[C:28](=[N:30][NH2:31])[N:29]=1.CN1CCOCC1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Cl:23][C:24]1[N:29]=[C:28]([NH:30][NH:31][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:32])=[C:26]([NH:33][CH2:34][C:35]([CH3:43])([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[CH3:36])[N:25]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 178448898HCID 178448898, compound

Product 1

HCID 86636982[(2R)-3-[2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)hydrazino]-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamideYield 35.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R)-3-Cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (0.238 g, 0.78 mmol), 2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4(1H)-pyrimidinone hydrazone (0.249 g), NMM (0.26 mL, 2.35 mmol), HOAt (0.106 g, 0.78 mmol), EDC (0.150 g, 0.78 mmol) and DMF (4 mL) were combined, and the solution was stirred overnight. Purification by RP-HPLC provided [(2R)-3-[2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)hydrazino]-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide as a brown oil (0.169 g). LCMS: (M+H)+=606.3.

Workup

  1. customPurification by RP-HPLC

Sources & evidence

ORD record
ord-4a7d3f7725d64fd0a16cfea11d607ab7
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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