Hydrochloric Acid → Ethyl 4-(2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylate

HRID 2361239노트

반응식

HRID 2361239 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([C:11]1[C:19]2[C:14](=[CH:15][C:16]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:17][CH:18]=2)[NH:13][CH:12]=1)[CH2:9][NH2:10].O=[CH:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].C1(C)C=CC=CC=1.Cl>O1CCOCC1.C(OCC)(=O)C.CCCCCC>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:11]2[C:19]3[C:14](=[CH:15][C:16]([N:20]4[CH2:21][CH2:22][O:23][CH2:24][CH2:25]4)=[CH:17][CH:18]=3)[NH:13][C:12]=2[C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:10][CH:9]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 70211Ethyl oxoacetateHCID 679947912-(2-Fluorophenyl)-2-(6-morpholino-1H-indol-3-yl)ethanamine

생성물 1

HCID 67994836Ethyl 4-(2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylate수율 41.6%

시약·촉매·용매 2

HCID 312751,4-Dioxane용매HCID 21226206Ethyl acetate hexane용매

실험 절차

To a solution of 2-(2-fluorophenyl)-2-(6-morpholino-1H-indol-3-yl)ethanamine (0.181 g, 0.533 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.233 mL, 1.173 mmol) in 1,4-dioxane (18 mL) at room temperature was added hydrogen chloride (4 N in 1,4-dioxane) (0.267 mL, 1.067 mmol). The solution turned heterogeneous and it was stirred at room temperature for 16 hr. The volatiles were removed under vacuum. The residue was diluted with water (20 mL), basified with saturated NaHCO3 solution to pH 10, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 ml), dried over anhydrous MgSO4, and concentrated to dryness under vacuum. To the residue were added toluene (10 mL) and 10% Pd/C (0.3 g), and the mixture was heated at 140° C. under an ambient atmosphere for 4.5 hr. The solid phase was removed by suction filtration. The filtrate was diluted with ethyl acetate (100 ml), washed with brine (25 ml), and dried over anhydrous MgSO4. The desired product (94 mg, 0.222 mmol, 41.6% yield) was isolated with ISCO (24 g silica gel, 30-60% ethyl acetate/hexane) as a tan solid.

후처리

  1. customThe volatiles were removed under vacuum
  2. additionThe residue was diluted with water (20 mL)
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. extractionThe combined extract
  5. washwas washed with brine (25 ml)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated to dryness under vacuum
  8. additionTo the residue were added toluene (10 mL) and 10% Pd/C (0.3 g)
  9. temperaturethe mixture was heated at 140° C. under an ambient atmosphere for 4.5 hr
  10. customThe solid phase was removed by suction filtration
  11. additionThe filtrate was diluted with ethyl acetate (100 ml)
  12. washwashed with brine (25 ml)
  13. dry with materialdried over anhydrous MgSO4

출처 및 근거

ORD 기록
ord-c76f8914e16744948ae4bd9e2cf6b024
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685969B2

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