1,2-Dichloroethane → [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(7S)-7-hydroxy-5-azaspiro[2.4]hept-5-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide

HRID 1366497Notes

Reaction equation

HRID 1366497 reaction equation
[F:1][C:2]1[C:3]([N:11]2[CH2:17][CH:16]([OH:18])[C:13]3([CH2:15][CH2:14]3)[CH2:12]2)=[N:4][C:5]([CH3:10])=[N:6][C:7]=1[NH:8][NH2:9].[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.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C=O)C>[CH:19]1([CH2:24][C@@H:25]([C:26]([NH:9][NH:8][C:7]2[C:2]([F:1])=[C:3]([N:11]3[CH2:17][C@@H:16]([OH:18])[C:13]4([CH2:14][CH2:15]4)[CH2:12]3)[N:4]=[C:5]([CH3:10])[N:6]=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 66936092HCID 66936092, compound

Product 1

HCID 86636963[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(7S)-7-hydroxy-5-azaspiro[2.4]hept-5-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamideYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(5-Fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-5-azaspiro[2.4]heptan-7-ol (82 mg, 0.324 mmol), (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (115 mg, 0.27 mmol), and HOAt (44 mg, 0.324 mmol) were dissolved in 2 mL of DMF. NMM (0.089 mL, 0.81 mmol) was added, followed by EDC (62 mg, 0.324 mmol). After stirring overnight at room temperature, the reaction mixture was purified by RP-HPLC to provide [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(7S)-7-hydroxy-5-azaspiro[2.4]hept-5-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (91 mg, 63%). LCMS: (M+H)+: 535.3.

Workup

  1. customthe reaction mixture was purified by RP-HPLC

Sources & evidence

ORD record
ord-29f63ca99e134bf88ed905c6363693d3
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…