Sodium Hydroxide → (6-Chloro-pyridin-3-yl)-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone

HRID 631902노트

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HRID 631902 반응식
Cl.Cl.[CH:3]1([N:7]2[CH2:13][CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.[OH-:14].[Na+].[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Cl)=[CH:19][N:18]=1>C(OC(C)C)(=O)C>[Cl:16][C:17]1[N:18]=[CH:19][C:20]([C:21]([N:10]2[CH2:11][CH2:12][CH2:13][N:7]([CH:3]3[CH2:6][CH2:5][CH2:4]3)[CH2:8][CH2:9]2)=[O:14])=[CH:23][CH:24]=1

참가 물질

5

반응물 3

HCID 14798Sodium Hydroxide2회HCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 574239521-Cyclobutyl-1,4-diazepane dihydrochloride

생성물 1

HCID 58076653(6-Chloro-pyridin-3-yl)-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone수율 91%

시약·촉매·용매 1

HCID 7915Isopropyl Acetate용매2회

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온도
7.5 °C

실험 절차

A 5-L, 3-necked, round-bottomed flask was equipped with a mechanical stirrer and a thermocouple and charged with 1-cyclobutyl-[1,4]diazepane dihydrochloride (110.0 g, 484.6 mmol), 1 N NaOH (1400 mL) and isopropyl acetate (600 mL). A pre-cooled (0° C.) solution of 6-chloronicotinyl chloride (82.7 g, 470.0 mmol) in isopropyl acetate (800 mL) was added via an addition funnel at a rate such that the reaction temperature was maintained between 5-10° C. After the addition was complete, the reaction mixture was warmed to rt and stirred for 2 h (pH of reaction mixture ca. 5.6). The reaction mixture was basified with 2 N NaOH(aq) (to pH ca. 13). The phases were separated and the aqueous layer was extracted with isopropyl acetate (2×300 mL). Some reddish-brown flocculent material was observed during the extractions. The organic layers were pooled and filtered through a pad of diatomaceous earth. The filtrate was washed with satd. aq. NaCl (1×300 mL) and dried over anhydrous Na2SO4. Filtration and removal of the solvent by rotary evaporation under reduced pressure afforded the crude product as a reddish brown oil (126.0 g, 91%). 1H-NMR (400 MHz, CDCl3) δ ppm: 8.45 (m, 1H), 7.74 (m, 1H), 7.39 (m, 1H), 3.86-3.76 (m, 2H), 3.53-3.45 (m, 2H), 3.05-2.80 (m, 1H), 2.70 (br s, 1H), 2.62-2.45 (m 3H), 2.10-1.56 (m, 8H). MS m/z (ESI+): 294.1 (M+H+). HPLC (Method B): Rt=6.06 min.

후처리

  1. additionwas added via an addition funnel at a rate such that the reaction temperature
  2. additionAfter the addition
  3. temperaturethe reaction mixture was warmed to rt
  4. custom(pH of reaction mixture ca. 5.6)
  5. customThe phases were separated
  6. extractionthe aqueous layer was extracted with isopropyl acetate (2×300 mL)
  7. extractionSome reddish-brown flocculent material was observed during the extractions
  8. filtrationfiltered through a pad of diatomaceous earth
  9. washThe filtrate was washed with satd
  10. dry with materialaq. NaCl (1×300 mL) and dried over anhydrous Na2SO4
  11. filtrationFiltration and removal of the solvent
  12. customby rotary evaporation under reduced pressure

출처 및 근거

ORD 기록
ord-4cd53ed68395432c9045da79a80b321a
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321729B2

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