tert-Butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate → 5-Oxo-2-(4-phenoxyphenyl)-7-(piperidin-4-yl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 64353Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 64353
[NH2:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:9][CH:8]=2)[C:3]=1[C:20]([NH2:22])=[O:21].C([O:25][C:26](=O)[CH2:27][C:28]([CH:30]1[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]1)=O)C>CC(O)=O>[O:25]=[C:26]1[CH:27]=[C:28]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[N:6]2[N:5]=[C:4]([C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)=[CH:11][CH:12]=3)[C:3]([C:20]([NH2:22])=[O:21])=[C:2]2[NH:1]1

Komponenten

4

Edukt 2

HCID 6618868tert-Butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylateHCID 178513497HCID 178513497, Verbindung

Produkt 1

HCID 1369280745-Oxo-2-(4-phenoxyphenyl)-7-(piperidin-4-yl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamideAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carboxamide (412 mg, 1.4 mmol) and tert-butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (420 mg, 1.4 mmol) in HOAc (20 mL) was stirred at 90° C. for 16 hr. The solvent was removed under vacuum, and the residue was partitioned between aq. NaHCO3 and ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by Pre-HPLC eluting from 25% to 90% CH3CN in 0.1% TFA in H2O. Fractions containing the desired product were combined and lyophilized overnight to afford 5-oxo-2-(4-phenoxyphenyl)-7-(piperidin-4-yl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamide (0.3 g, 50%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.71 (br s, 1H), 8.68-8.65 (m, 1H), 8.42-8.39 (m, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.47-7.41 (m, 2H), 7.22-7.18 (m, 1H), 7.14-7.09 (m, 4H), 5.72 (s, 1H), 3.50-3.35 (m, 2H), 3.17-3.06 (m, 1H), 3.01-2.87 (m, 2H), 2.15-2.05 (m, 2H), 1.83-1.72 (m, 2H). MS (ESI) m/e [M+1]+ 430.1.

Aufarbeitung

  1. customThe solvent was removed under vacuum
  2. customthe residue was partitioned between aq. NaHCO3 and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by Pre-HPLC
  7. washeluting from 25% to 90% CH3CN in 0.1% TFA in H2O
  8. additionFractions containing the desired product
  9. waitlyophilized overnight

Quellen und Nachweise

ORD-Eintrag
ord-c6a7b0f2b34245b98ad6e3b13a3e7205
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447106B2

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