Hydrochloric Acid → 5-{[6-(4-Cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}-2-furoic acid

HRID 421803Notes

Reaction equation

HRID 421803 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]([CH2:15][C:16]3[O:20][C:19]([C:21]([O:23]C)=[O:22])=[CH:18][CH:17]=3)[C:13](=[O:25])[N:12]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=3)[C:11]([CH3:36])=[C:10]2[C:37]([CH:39]2[CH2:41][CH2:40]2)=[O:38])=[CH:5][CH:4]=1)#[N:2].[OH-].[Li+].Cl.CO>O1CCCC1.O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]([CH2:15][C:16]3[O:20][C:19]([C:21]([OH:23])=[O:22])=[CH:18][CH:17]=3)[C:13](=[O:25])[N:12]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:33])([F:34])[F:35])[CH:27]=3)[C:11]([CH3:36])=[C:10]2[C:37]([CH:39]2[CH2:40][CH2:41]2)=[O:38])=[CH:5][CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium Hydroxide2×HCID 59684838Methyl 5-{[6-(4-cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}-2-furoate

Product 1

HCID 596848375-{[6-(4-Cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}-2-furoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of methyl 5-{[6-(4-cyanophenyl)-5-(cyclopropylcarbonyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]methyl}-2-furoate (Example 42) (50 mg, 0.09 mmol) in tetrahydrofuran (1.5 ml) is treated with a solution of lithium hydroxide (2.34 mg, 0.1 mmol) in water (1.5 ml). After three hours stirring at room temperature, additional lithium hydroxide (2.34 mg, 0.1 mmol) is added. The reaction solution is stirred overnight (16 h), then allowed to stand for 48 h. The solution is acidified with 1 N hydrochloric acid (500 μl). After 5 minutes stirring, a precipitate is obtained. Methanol (3 ml) is added, and the crude reaction solution is purified directly by preparative HPLC (RP18 column; eluent: acetonitrile/water 30:70→90:10). The title compound is isolated as a brownish solid.

Workup

  1. stirringThe reaction solution is stirred overnight (16 h)
  2. waitto stand for 48 h
  3. stirringAfter 5 minutes stirring
  4. customa precipitate is obtained
  5. customthe crude reaction solution
  6. customis purified directly by preparative HPLC (RP18 column; eluent: acetonitrile/water 30:70→90:10)

Sources & evidence

ORD record
ord-29253d58080a4584b03c988d5aeafe5b
Source dataset
uspto-grants-2012_01
Patent number
US08101615B2

Reaction notes

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