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 2194768ノート

反応式

HRID 2194768 の反応式
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]

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water触媒HCID 8028Tetrahydrofuran溶媒

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-7860247e46c54b279bb22c0b6fb98a1a
出典データセット
uspto-grants-2012_12
特許番号
US08334295B2

反応ノート

読み込み中…