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

HRID 1366684Notes

Reaction equation

HRID 1366684 reaction equation
Cl.Cl.[F:3][C:4]1[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])=[N:6][C:7]([CH3:12])=[N:8][C:9]=1[NH:10][NH2:11].[CH:20]([OH:23])([CH3:22])C.CN1[CH2:30][CH2:29][O:28]CC1.ON1[C:36]2N=[CH:38][CH:39]=[CH:40][C:35]=2N=N1.[CH2:41](Cl)[CH2:42]Cl.[CH3:45][N:46]([CH:48]=[O:49])C>>[CH:41]1([CH2:42][C@@H:22]([C:20]([NH:11][NH:10][C:9]2[C:4]([F:3])=[C:5]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]3[CH3:19])[N:6]=[C:7]([CH3:12])[N:8]=2)=[O:23])[CH2:45][N:46]([O:28][CH2:29][C:30]2[CH:36]=[CH:35][CH:40]=[CH:39][CH:38]=2)[CH:48]=[O:49])[CH2:39][CH2:40][CH2:35][CH2:36]1

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 3776IsopropanolHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 181649HOAtHCID 66936365(3S)-4-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-3-methylmorpholine dihydrochloride

Product 1

HCID 86637030[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamideYield 93%

Procedure

To a solution of (3S)-4-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-3-methyl morpholine dihydrochloride (251.5 mg, 0.752 mmol) in DMF (6 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid, N,N-diisopropylethylamine salt, isopropanol solvate (306.1 mg, 0.619 mmol), N-methylmorpholine (0.410 ml, 3.73 mmol), 1-hydroxy-7-azabenzotriazole (0.101 g, 0.742 mmol), and EDC (0.142 g, 0.741 mmol). The solution was allowed to stir overnight, and was then purified directly by Gilson RPLC to give [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide (314.6 mg, 93%) as an orange foam. LCMS: (M+H)+: 549.2.

Workup

  1. customwas then purified directly by Gilson RPLC

Sources & evidence

ORD record
ord-64b3a1915d624082b23699b5e57afa60
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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