Diisopropylethylamine → (S)-N-cyclopropyl-3-methyl-4-(4-((6-oxo-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3',2'-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide

온도

90 °C

(S)-3-(hydroxymethyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazin-6(6aH)-one (100 mg, 0.429 mmol), N-cyclopropyl-3-methyl-4-(piperazin-1-yl)benzamide dihydrochloride (143 mg, 0.430 mmol), (cyanomethyl)trimethylphosphonium iodide (167 mg, 0.686 mmol) and N,N-diisopropylethylamine (374 μl, 2.143 mmol) were suspended in Propiononitrile (Volume: 1287 μl) and heated in a closed vial at 90° C. for 4 h. The reaction mixture became a dark brown solution. It was cooled to room temperature and purified using HPLC (NH4HCO3 buffered, 20-70% ACN in water). The fractions were concentrated in vacuo and the resulting solid was recrystallized from MeCN (20 mL), filtered off, washed with water (2 mL) and dried in vacuum to afford (S)—N-cyclopropyl-3-methyl-4-(4-((6-oxo-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide (50.7 mg, 0.107 mmol, 24.92% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.49-0.59 (m, 2 H) 0.60-0.71 (m, 2 H) 1.33-1.57 (m, 3 H) 1.64 (d, J=12.88 Hz, 1 H) 1.85 (d, J=12.63 Hz, 1 H) 2.04 (d, J=12.88 Hz, 1 H) 2.25 (s, 3 H) 2.42-2.56 (m, 4 H) 2.60 (td, J=12.63, 2.78 Hz, 1 H) 2.76-2.93 (m, 5 H) 3.38 (s, 2 H) 3.84 (dd, J=11.37, 2.78 Hz, 1 H) 4.50 (d, J=13.14 Hz, 1 H) 6.98 (d, J=2.02 Hz, 1 H) 7.00 (d, J=8.34 Hz, 1 H) 7.56-7.63 (m, 2 H) 7.66 (d, J=2.02 Hz, 1 H) 8.22 (d, J=4.29 Hz, 1 H) 10.49 (s, 1 H); [M+H] calc'd for C27H34N6O2, 475; found, 475.

1. temperatureIt was cooled to room temperature
2. custompurified
3. concentrationThe fractions were concentrated in vacuo
4. customthe resulting solid was recrystallized from MeCN (20 mL)
5. filtrationfiltered off
6. washwashed with water (2 mL)
7. customdried in vacuum

ORD 기록

ord-b22ba83e74bf4ba9967e5f287fbc2fba

출처 데이터셋

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08822470B2