2,4,6-Trichloropyrimidine → 2-(2,6-Dichloropyrimidin-4-ylamino)-4-methylpentanoic acid (3-ethoxypropyl)amide

HRID 1822812Notes

Reaction equation

HRID 1822812 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([Cl:9])[N:3]=1.Cl.[CH2:11]([O:13][CH2:14][CH2:15][CH2:16][NH:17][C:18](=[O:25])[C@H:19]([CH2:21][CH:22]([CH3:24])[CH3:23])[NH2:20])[CH3:12].C(N(CC)C(C)C)(C)C>CS(C)=O.C(OCC)(=O)C>[CH2:11]([O:13][CH2:14][CH2:15][CH2:16][NH:17][C:18](=[O:25])[CH:19]([NH:20][C:6]1[CH:5]=[C:4]([Cl:9])[N:3]=[C:2]([Cl:1])[N:7]=1)[CH2:21][CH:22]([CH3:23])[CH3:24])[CH3:12]

Participants

6

Reactant 3

HCID 773782,4,6-TrichloropyrimidineHCID 81531DiisopropylethylamineHCID 23568571L-leucine-3-ethoxypropylamide hydrochloride

Product 1

HCID 235685972-(2,6-Dichloropyrimidin-4-ylamino)-4-methylpentanoic acid (3-ethoxypropyl)amide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2,4,6-trichloropyrimidine (1.0 g), L-leucine-3-ethoxypropylamide hydrochloride (17 mL of a 0.32 M solution in DMSO), and N,N-diisopropylethylamine (3.0 mL) were stirred for 24 h in 20 mL methyl sulfoxide at 60 C. The solution was cooled to room temperature and diluted with ethyl acetate (100 mL), then washed 4 times with 100 mL aliquots of a saturated aqueous solution of sodium chloride. Silica gel chromatography (gradient: 20–40–50–100% ethyl acetate in hexanes) followed by semi-preparative HPLC purification of mixed fractions provided 1.06 g of 2-(2,6-dichloropyrimidin-4-ylamino)-4-methylpentanoic acid (3-ethoxypropyl)amide as a colorless oil

Workup

  1. washwashed 4 times with 100 mL aliquots of a saturated aqueous solution of sodium chloride
  2. customSilica gel chromatography (gradient: 20–40–50–100% ethyl acetate in hexanes) followed by semi-preparative HPLC purification of mixed fractions

Sources & evidence

ORD record
ord-df2f68b698644279bacdb87b28e22015
Source dataset
uspto-grants-2006_05
Patent number
US07037916B2

Reaction notes

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