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

HRID 1366421Notes

Reaction equation

HRID 1366421 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:23]([C:25]1[N:30]=[C:29]([NH:31][NH2:32])[C:28]([F:33])=[C:27]([N:34]2[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]2)[N:26]=1)[CH3:24].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CN1CCOCC1>CN(C=O)C.O>[CH:1]1([CH2:6][C@@H:7]([C:8]([NH:32][NH:31][C:29]2[C:28]([F:33])=[C:27]([N:34]3[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]3)[N:26]=[C:25]([CH2:23][CH3:24])[N:30]=2)=[O:10])[CH2:11][N:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[O:22])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 669359752-Ethyl-5-fluoro-4-hydrazino-6-(4-methyl-1-piperazinyl)pyrimidine

Product 1

HCID 86636931((2R)-2-(Cyclopentylmethyl)-3-{2-[2-ethyl-5-fluoro-6-(4-methyl-1-piperazinyl)-4-pyrimidinyl]hydrazino}-3-oxopropyl)[(phenylmethyl)oxy]formamideYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (12.4 g, 40.6 mmol) in DMF (120 mL) was added to a mixture of 2-ethyl-5-fluoro-4-hydrazino-6-(4-methyl-1-piperazinyl)pyrimidine (9.6 g, 37.8 mmol), HOAt (5.66 g, 41.58 mmol), and EDC (7.97 g, 41.58 mmol). The resulting solution was treated with NMM (9.1 mL, 83.2 mmol) and stirred at room temperature for 3 h. After the reaction was complete, 200 mL of water was added and the solution was extracted three times with 200 mL of ether. The combined organic layers were washed with water (200 mL) and brine (100 mL), and then dried over anhydrous Na2SO4. Evaporation of the solvent provided a light yellow glassy solid as the pure product (17.1 g, 84%).

Workup

  1. extractionthe solution was extracted three times with 200 mL of ether
  2. washThe combined organic layers were washed with water (200 mL) and brine (100 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. customEvaporation of the solvent

Sources & evidence

ORD record
ord-03d79562b58c44878514967ab93f0830
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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