Diisopropylethylamine → 2-(6-Butyl-2-chloropyrimidin-4-ylamino)-4-methypentanoic acid (3-ethoxypropyl)amide

HRID 1822791Notes

Reaction equation

HRID 1822791 reaction equation
[CH2:1]([C:5]1[N:10]=[C:9]([Cl:11])[N:8]=[C:7](Cl)[CH:6]=1)[CH2:2][CH2:3][CH3:4].Cl.[CH2:14]([O:16][CH2:17][CH2:18][CH2:19][NH:20][C:21](=[O:28])[C@H:22]([CH2:24][CH:25]([CH3:27])[CH3:26])[NH2:23])[CH3:15].C(N(CC)C(C)C)(C)C>CS(C)=O.C(OCC)(=O)C>[CH2:14]([O:16][CH2:17][CH2:18][CH2:19][NH:20][C:21](=[O:28])[CH:22]([NH:23][C:7]1[CH:6]=[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])[N:10]=[C:9]([Cl:11])[N:8]=1)[CH2:24][CH:25]([CH3:26])[CH3:27])[CH3:15]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 141179454-Butyl-2,6-dichloropyrimidineHCID 23568571L-leucine-3-ethoxypropylamide hydrochloride

Product 1

HCID 235686202-(6-Butyl-2-chloropyrimidin-4-ylamino)-4-methypentanoic acid (3-ethoxypropyl)amide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

6-Butyl-2,4-dichloropyrimidine (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 1.24 g of 2-(6-butyl-2-chloropyrimidin-4-ylamino)-4-methypentanoic 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-1b5b9c5a0ee644dbbd998795cdef71dd
Source dataset
uspto-grants-2006_05
Patent number
US07037916B2

Reaction notes

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