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

HRID 1366389Notes

Reaction equation

HRID 1366389 reaction equation
[N:1]1([C:5]2[C:10]([F:11])=[C:9]([NH:12][NH2:13])[N:8]=[C:7]([CH2:14][CH3:15])[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH:16]1([CH2:21][C@H:22]([CH2:26][N:27]([CH:36]=[O:37])[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:23](O)=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17]1.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C=O)C>[N:1]1([C:5]2[N:6]=[C:7]([CH2:14][CH3:15])[N:8]=[C:9]([NH:12][NH:13][C:23](=[O:24])[C@H:22]([CH2:21][CH:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[CH2:26][N:27]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:36]=[O:37])[C:10]=2[F:11])[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 669360004-(1-Azetidinyl)-2-ethyl-5-fluoro-6-hydrazinopyrimidine

Product 1

HCID 86636917[(2R)-3-{2-[6-(1-azetidinyl)-2-ethyl-5-fluoro-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamideYield 76.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(1-Azetidinyl)-2-ethyl-5-fluoro-6-hydrazinopyrimidine (88 mg, 0.42 mmol), (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (140 mg, 0.46 mmol), and HOAt (56 mg, 0.42 mmol) were dissolved in 3 mL of DMF. Then, NMM (71 μL, 0.65 mmol) was added, followed by EDC (75 mg, 0.40 mmol). After stirring overnight at room temperature, the reaction mixture was purified by RP-HPLC to provide [(2R)-3-{2-[6-(1-azetidinyl)-2-ethyl-5-fluoro-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (160 mg, 76%). LCMS: (M+H)+: 499.4.

Workup

  1. customthe reaction mixture was purified by RP-HPLC

Sources & evidence

ORD record
ord-9bf8c214bda14da4a8a36deaec63b9b6
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…