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 1366507Notes

Reaction equation

HRID 1366507 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:14][CH:13]([OH:15])[C:10]3([CH2:12][CH2:11]3)[CH2:9]2)[C:5]([F:16])=[C:4]([NH:17][NH2:18])[N:3]=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.[CH:40]1C=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:18][NH:17][C:4]2[C:5]([F:16])=[C:6]([N:8]3[CH2:14][C@@H:13]([OH:15])[C:10]4([CH2:12][CH2:11]4)[CH2:9]3)[N:7]=[C:2]([CH3:40])[N:3]=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 866369665-(2-Chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-5-azaspiro[2.4]heptan-7-ol

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 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(2-Chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-5-azaspiro[2.4]heptan-7-ol (167 mg 0.610 mmol), (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (217 mg, 0.508 mmol), and HOAt (83 mg, 0.610 mmol) were dissolved in 5 mL of DMF. NMM (0.167 mL, 1.525 mmol) was added, followed by EDC (117 mg, 0.6101 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 (223 mg, 79%). LCMS: (M+H)+: 555.3.

Workup

  1. customthe reaction mixture was purified by RP-HPLC

Sources & evidence

ORD record
ord-a09874fd13f64574ab3f5dbc3198066e
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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