Lithium Hydroxide → {1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid

HRID 2194768Notes

Reaction equation

HRID 2194768 reaction equation
C[O:2][C:3](=[O:31])[CH2:4][C:5]1([CH2:8][N:9]2[C:14]([C:15](=[O:25])[C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([C:23]#[N:24])[CH:17]=3)=[C:13]([CH:26]([CH3:28])[CH3:27])[C:12](=[O:29])[NH:11][C:10]2=[O:30])[CH2:7][CH2:6]1.[OH-].[Li+]>C1COCC1.O>[C:23]([C:18]1[CH:17]=[C:16]([CH:21]=[C:20]([CH3:22])[CH:19]=1)[C:15]([C:14]1[N:9]([CH2:8][C:5]2([CH2:4][C:3]([OH:31])=[O:2])[CH2:6][CH2:7]2)[C:10](=[O:30])[NH:11][C:12](=[O:29])[C:13]=1[CH:26]([CH3:28])[CH3:27])=[O:25])#[N:24]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 25214958Methyl 2-[1-[[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-pyrimidin-1-yl]methyl]cyclopropyl]acetate

Product 1

HCID 25215194{1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acidYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of {1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid methyl ester (170 mg, 0.4 mmol) in THF (4 mL), were added lithium hydroxide (20 mg, 0.8 mmol) and two drops of water. The mixture was then refluxed for 2 hr. After cooling to room temperature, the mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, from ethyl acetate to 20% methanol in ethyl acetate) to give 100 mg (62%) of {1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid (83) as a white solid. m.p. 244-245° C.; 1H-NMR (500 MHz, DMSO-d6) δ 0.21-0.26 (2H, m), 0.34-0.36 (1H, m), 0.46-0.48 (1H, m), 0.98 (3H, d, J=6.8 Hz), 1.08 (3H, d, J=6.8 Hz), 2.06-2.12 (2H, m), 2.23 (1H, d, J=17.0 Hz), 2.44 (3H, s), 3.32 (1H, d, J=15.0 Hz), 3.74 (1H, d, J=15.0 Hz), 8.08 (1H, s), 8.19 (1H, s), 8.43 (1H, s), 11.45 (1H, s), 12.02 (1H, br. s); m/z (EI) 409 (M+).

Workup

  1. temperatureThe mixture was then refluxed for 2 hr
  2. customthe mixture was evaporated in vacuo
  3. customthe residue was purified by silica gel column chromatography (eluent, from ethyl acetate to 20% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-7860247e46c54b279bb22c0b6fb98a1a
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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