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 2194768노트

반응식

HRID 2194768 반응식
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]

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water촉매HCID 8028Tetrahydrofuran용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-7860247e46c54b279bb22c0b6fb98a1a
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08334295B2

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