Diisopropylethylamine → (S)-3-((4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)methyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3',2'-e]pyrazin-6(6aH)-on

HRID 69625

반응식

HRID 69625 반응식
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][CH2:15][CH2:16][C@H:8]3[C:7](=[O:17])[NH:6][C:5]=2[CH:4]=1.[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C.Cl.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[CH2:44][CH2:45][NH:46][CH2:47][CH:48]=2)=[CH:39][CH:38]=1>C(#N)CC.CCO.O>[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[CH2:48][CH2:47][N:46]([CH2:2][C:3]3[CH:12]=[N:11][C:10]4[N:9]5[CH2:13][CH2:14][CH2:15][CH2:16][C@H:8]5[C:7](=[O:17])[NH:6][C:5]=4[CH:4]=3)[CH2:45][CH:44]=2)=[CH:39][CH:38]=1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 27236124-(4-Chlorophenyl)-1,2,3,6-tetrahydropyridinium chlorideHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 58324368(S)-3-(hydroxymethyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3',2'-e]pyrazin-6(6aH)-one

생성물 1

HCID 58324425(S)-3-((4-(4-chlorophenyl)-5,6-dihydropyridin-1(2H)-yl)methyl)-7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3',2'-e]pyrazin-6(6aH)-on수율 43%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 7854Propionitrile용매

반응 조건

온도
90 °C

실험 절차

(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) was suspended in propionitrile (1 mL) and (cyanomethyl)trimethylphosphonium iodide (125.0 mg, 0.51 mmol) was added followed by N-ethyl-N-isopropylpropan-2-amine (225 ul, 1.3 mmol). To the stirred mixture was then added 4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine hydrochloride (109 mg, 0.472 mmol). The reaction was heated to 90° C. with stirring for 16 h. The reaction was then cooled to room temperature, diluted with EtOH (3 ml) and water (˜300 ul), then filtered. The solids were collected and refluxed in ethanol (5 mL) for 2 h. The suspension was cooled back to room temperature and filtered. The precipitate was filtered off and dried in vacuum to afford the title compound (75.1 mg, 43%) as a white solid. 1H NMR (DMSO-d6) δ (ppm): 10.47 (s, 1H), 7.66 (d, J=1.8 Hz, 1H), 7.40-7.48 (m, 2H), 7.34-7.40 (m, 2H), 6.98 (d, J=2.0 Hz, 1H), 6.18 (s, 1H), 4.45-4.55 (m, 1H), 3.84 (d, J=11.4 Hz, 1H), 3.42 (s, 2H), 3.01 (d, J=2.8 Hz, 2H), 2.56-2.66 (m, 3H), 2.44 (br. s., 2H), 1.98-2.08 (m, 1H), 1.80-1.89 (m, 1H), 1.59-1.68 (m, 1H), 1.34-1.57 (m, 3H). [M+H] calc'd for C23H25ClN4O, 409; found, 409. MP: 201.6° C.

후처리

  1. temperatureThe reaction was then cooled to room temperature
  2. filtrationfiltered
  3. customThe solids were collected
  4. temperaturerefluxed in ethanol (5 mL) for 2 h
  5. temperatureThe suspension was cooled back to room temperature
  6. filtrationfiltered
  7. filtrationThe precipitate was filtered off
  8. customdried in vacuum

출처 및 근거

ORD 기록
ord-c40d9ce3306f4895b0536f8da1b59e90
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822470B2

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