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 2194768Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2194768
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]

Komponenten

5

Edukt 2

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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+).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-7860247e46c54b279bb22c0b6fb98a1a
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08334295B2

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