1,2-Dichloroethane → [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-(methylthio)-6-[(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide

HRID 1366634Notes

Reaction equation

HRID 1366634 reaction equation
[F:1][C:2]1[C:3](=[N:17][NH2:18])[N:4]=[C:5]([S:15][CH3:16])[NH:6][C:7]=1[NH:8][CH2:9][C:10]1[S:11][CH:12]=[CH:13][N:14]=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.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[CH:19]1([CH2:24][C@@H:25]([C:26]([NH:18][NH:17][C:3]2[C:2]([F:1])=[C:7]([NH:8][CH2:9][C:10]3[S:11][CH:12]=[CH:13][N:14]=3)[N:6]=[C:5]([S:15][CH3:16])[N:4]=2)=[O:27])[CH2:29][N:30]([O:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)[CH:38]=[O:39])[CH2:23][CH2:22][CH2:21][CH2:20]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 178503508HCID 178503508, compound

Product 1

HCID 86637015[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-(methylthio)-6-[(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamideYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Fluoro-2-(methylthio)-6-[(1,3-thiazol-2-ylmethyl)amino]-4(1H)-pyrimidinone hydrazone (0.1958 g, 0.685 mmol) and (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (0.355 g, 0.823 mmol) were dissolved in DMF (5 mL). NMM (0.30 mL, 2.7286 mmol) was added, followed by HOAt (0.112 g, 0.824 mmol) and EDC (0.157 g, 0.819 mmol). After stirring overnight, the reaction mixture was purified by RP-HPLC to provide [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-(methylthio)-6-[(1,3-thiazol-2-ylmethyl)amino]-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide as an orange solid (0.2197 g, 57%). LCMS: (M+H)+=568.2.

Workup

  1. customthe reaction mixture was purified by RP-HPLC

Sources & evidence

ORD record
ord-dd1de7e90ee945a98ab5db0d04a76b81
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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