Hydrochloric Acid → 3-{3-[(E)-2-Carboxyvinyl]benzyl}-4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)-phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

HRID 1366255Notes

Reaction equation

HRID 1366255 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([O:17]CC)=[O:16])=[C:13]([CH3:20])[N:12]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:11](=[O:31])[N:10]2[CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[C:35](/[CH:39]=[CH:40]/[C:41]([O:43]CC)=[O:42])[CH:34]=2)=[CH:5][CH:4]=1)#[N:2].[OH-].[Na+].C(O)C.Cl>O1CCCC1.O>[C:41](/[CH:40]=[CH:39]/[C:35]1[CH:34]=[C:33]([CH:38]=[CH:37][CH:36]=1)[CH2:32][N:10]1[CH:9]([C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=2)[C:14]([C:15]([OH:17])=[O:16])=[C:13]([CH3:20])[N:12]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:30])[F:29])[CH:22]=2)[C:11]1=[O:31])([OH:43])=[O:42]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14798Sodium HydroxideHCID 59411321Ethyl 4-(4-cyanophenyl)-3-{3-[(1E)-3-ethoxy-3-oxoprop-1-en-1-yl]benzyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Product 1

HCID 594112783-{3-[(E)-2-Carboxyvinyl]benzyl}-4-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)-phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 4-(4-cyanophenyl)-3-{3-[(1E)-3-ethoxy-3-oxoprop-1-en-1-yl]benzyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (Example 37) (50 mg, 0.08 mmol) in tetrahydrofuran (2 ml) is added a solution of sodium hydroxide (32.4 mg, 0.8 mmol) in water (0.5 ml). After stirring at room temperature for 1 hour, ethanol (2 ml) is added. After 16 hours stirring, the pH of the solution is adjusted to 2 with 1 N hydrochloric acid, and the product is extracted with ethyl acetate (3×100 ml). The combined organic phases are washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude product is purified by preparative HPLC (RP18 column; eluent: acetonitrile/0.1% aq. formic acid 10:90→90:10). The title compound is obtained as a colourless solid.

Workup

  1. stirringAfter 16 hours stirring
  2. extractionthe product is extracted with ethyl acetate (3×100 ml)
  3. washThe combined organic phases are washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product is purified by preparative HPLC (RP18 column; eluent: acetonitrile/0.1% aq. formic acid 10:90→90:10)

Sources & evidence

ORD record
ord-b46eb9af02f4457fa6507eb1aa21d515
Source dataset
uspto-grants-2011_02
Patent number
US07893073B2

Reaction notes

Loading…