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Hydrochloric Acid → N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamide

HRID 538093
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HRID 538093 반응식
[Br-].[C:2]([CH2:4][CH2:5][CH2:6][CH2:7][Zn+])#[N:3].Cl[C:10]1[N:15]=[N:14][C:13]([NH:16][C:17](=[O:25])[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][CH:11]=1.Cl>CCOC(C)=O.Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[C:2]([CH2:4][CH2:5][CH2:6][CH2:7][C:10]1[N:15]=[N:14][C:13]([NH:16][C:17](=[O:25])[CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:12][CH:11]=1)#[N:3]
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참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 86687867N-(6-chloropyridazin-3-yl)-2-phenylacetamideHCID 178510995HCID 178510995, 화합물

생성물 1

HCID 86687868N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamide수율 60.2%

시약·촉매·용매 2

HCID 178418745HCID 178418745, 화합물촉매
HCID 8857
Ethyl Acetate
용매
2회

반응 조건

온도
19 °C

실험 절차

A 1000 mL three-neck flask fitted with internal temperature probe and addition funnel was flushed with Ar(g). Under positive Argon pressure 4-cyanobutylzinc bromide (0.5M in THF, 500 mL, 250 mmol) was charged into the addition funnel then added to the reaction vessel at room temperature. Solid N-(6-chloropyridazin-3-yl)-2-phenylacetamide (20.6 g, 83.3 mmol) was added to the stirred solution at RT under Ar(g) flow, followed by the addition of NiCl2(dppp) (4.52 g, 8.33 mmol). The resulting mixture was stirred at 19° C. for 240 minutes and then quenched with ethanol (120 mL). Water (380 mL) added to the stirred red solution, giving a thick precipitate. Ethyl acetate (760 mL) added and stirred well for 30 minutes. The solids were removed by filtration through a pad of celite. The mother liquor was then transferred to a separatory funnel and the organic layer was washed with H2O (380 mL), 0.5% ethylenediaminetetraacetic acid solution (380 mL) and again with H2O (380 mL). The organic layer was concentrated by rotoevaporation. Resulting red oil was redissolved in EtOAc (200 mL) and 1M HCl (380 mL) was added to the well stirred flask. After 30 minutes the mixture was transferred to separatory funnel and the aqueous layer collected. The organic layer was extracted with 1M HCl (2×380 mL). The aqueous layer's pH was then adjusted to ˜7 using 7.5% sodium bicarbonate solution and the pale yellow precipitate was collected by suction filtration, rinsed with water (200 mL) and diethyl ether (2×200 mL). The solid was dried overnight under high vacuum to afford N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamide (1023, 14.76 g). 1H NMR (300 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.23 (d, J=9.036 Hz, 1H), 7.59 (d, J=9.246 Hz, 1H), 7.32 (m, 5H), 3.79 (s, 2H), 2.90 (t, J=7.357 Hz, 2H), 2.56 (t, J=7.038 Hz, 2H), 1.79 (t, J=7.311 Hz, 2H), 1.63 (t, J=7.01 Hz, 2H)

후처리

  1. customA 1000 mL three-neck flask fitted with internal temperature probe and addition funnel
  2. customwas flushed with Ar(g)
  3. additionthen added to the reaction vessel at room temperature
  4. customquenched with ethanol (120 mL)
  5. additionWater (380 mL) added to the stirred red solution
  6. customgiving a thick precipitate
  7. stirringstirred well for 30 minutes
  8. customThe solids were removed by filtration through a pad of celite
  9. customThe mother liquor was then transferred to a separatory funnel
  10. washthe organic layer was washed with H2O (380 mL), 0.5% ethylenediaminetetraacetic acid solution (380 mL) and again with H2O (380 mL)
  11. concentrationThe organic layer was concentrated by rotoevaporation
  12. customResulting red oil
  13. stirringstirred flask
  14. waitAfter 30 minutes the mixture was transferred to separatory funnel
  15. customthe aqueous layer collected
  16. extractionThe organic layer was extracted with 1M HCl (2×380 mL)
  17. filtrationthe pale yellow precipitate was collected by suction filtration
  18. washrinsed with water (200 mL) and diethyl ether (2×200 mL)
  19. customThe solid was dried overnight under high vacuum

출처 및 근거

ORD 기록
ord-bac1611d05a6442b9bf2e3676d741029
출처 데이터셋
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08865718B2

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