Triethylamine → (R)-methyl 3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoate

HRID 2062154Notes

Reaction equation

HRID 2062154 reaction equation
C(O[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:25])[C@H:18]([OH:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.ClC1[C:36]2[C:31](=[CH:32][C:33]([CH3:37])=[CH:34][CH:35]=2)[N:30]=[C:29]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[OH:44])[N:28]=1.C(N(CC)CC)C>[Pd].CO>[OH:24][C@@H:18]([C:17]([N:14]1[CH2:13][CH2:12][N:11]([C:9]2[C:36]3[C:31](=[CH:32][C:33]([CH3:37])=[CH:34][CH:35]=3)[N:30]=[C:29]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[OH:44])[N:28]=2)[CH2:16][CH2:15]1)=[O:25])[CH2:19][C:20]([O:22][CH3:23])=[O:21]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 58010639HCID 58010639, compoundHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 136121665(R)-methyl 3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoateYield 57%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

4-((R)-2-Hydroxy-3-methoxycarbonyl-propionyl)-piperazine-1-carboxylic acid benzyl ester (0.52 g, 1.5 mmol) and MeOH (15 mL) were stirred with 10% Pd/C under an H2 atmosphere at ambient pressure overnight. After filtration and evaporation of the solvent the residue was taken up in CH2Cl2, and 2-(4-chloro-7-methylquinazolin-2-yl)phenol (0.40 g, 1.50 mmol) plus triethylamine (0.41 mL, 3.00 mmol) were added. The reaction mixture was stirred at room temperature overnight, washed with water, dried over Na2SO4, and concentrated. Purification via silica gel chromatography using 0-10% MeOH/CH2Cl2 provided (R)-methyl 3-hydroxy-4-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-oxobutanoate (0.38 g, 57%). LC/MS: m/z 451.1 (M+H)+ at 2.18 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. filtrationAfter filtration and evaporation of the solvent the residue
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-4af79d5654564bff87b43229bf9010f8
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

Loading…