1,2-Dichloroethane → [(2R)-3-{2-[2-chloro-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy) formamide

HRID 1366394Notes

Reaction equation

HRID 1366394 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][NH2:9])[C:5]([F:10])=[C:4]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[N:3]=1.[CH:18]1([CH2:23][C@H:24]([CH2:28][N:29]([CH:37]=[O:38])[O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[C:25](O)=[O:26])[CH2:22][CH2:21][CH2:20][CH2:19]1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CN1CCOCC1>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][NH:9][C:25](=[O:26])[C@H:24]([CH2:23][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22]2)[CH2:28][N:29]([O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[CH:37]=[O:38])[C:5]([F:10])=[C:4]([N:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)[N:3]=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 866369192-Chloro-5-fluoro-4-hydrazino-6-(4-methyl-1-piperazinyl)pyrimidine

Product 1

HCID 86636920[(2R)-3-{2-[2-chloro-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy) formamideYield 46.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-chloro-5-fluoro-4-hydrazino-6-(4-methyl-1-piperazinyl)pyrimidine (31 mg, 0.12 mmol), (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (36 mg, 0.12 mmol), HOAt (20 mg, 0.144 mmol), EDC (28 mg, 0.144 mmol) and NMM (26 uL, 0.144 mmol) in DMF (2 mL) was stirred until the reaction was complete (2 h). The reaction mixture was then purified via RP-HPLC to provide [(2R)-3-{2-[2-chloro-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl](tetrahydro-2H-pyran-2-yloxy)formamide (30 mg, 46%). LCMS: (M+H)+: 542.3; (M+Na)+: 564.3.

Workup

  1. custom(2 h)
  2. customThe reaction mixture was then purified via RP-HPLC

Sources & evidence

ORD record
ord-4abc84797b634c4dbae47afcb097c2a9
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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