Hydrochloric Acid → 2-(1-aminocyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride

HRID 1056149노트

반응식

HRID 1056149 반응식
C(OC([NH:8][C:9]1([C:12]2[NH:13][C:14]([C:22]3[C:31]([F:32])=[CH:30][CH:29]=[C:28]4[C:23]=3[N:24]=[C:25]([NH:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:26]([CH3:33])=[N:27]4)=[CH:15][C:16]=2[C:17]([O:19]CC)=[O:18])[CH2:11][CH2:10]1)=O)(C)(C)C.[ClH:39]>O1CCOCC1.O.CCOCC>[ClH:39].[NH2:8][C:9]1([C:12]2[NH:13][C:14]([C:22]3[C:31]([F:32])=[CH:30][CH:29]=[C:28]4[C:23]=3[N:24]=[C:25]([NH:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:26]([CH3:33])=[N:27]4)=[CH:15][C:16]=2[C:17]([OH:19])=[O:18])[CH2:10][CH2:11]1

참가 물질

6

반응물 2

HCID 313Hydrochloric AcidHCID 89783968ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate

생성물 1

HCID 897832122-(1-aminocyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride수율 95%

시약·촉매·용매 3

HCID 962Water용매2회HCID 3283Diethyl Ether용매HCID 312751,4-Dioxane용매3회

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온도
110 °C

실험 절차

A glass microwave reaction vessel was charged with ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (295b) (230 mg, 0.44 mmol) and LiOH monohydrate (Sigma-Aldrich) (184 mg, 4.38 mmol) in dioxane (1.5 mL) and water (0.75 mL). The reaction mixture was heated at 110° C. for 17 h. After cooling to RT, the reaction mixture was diluted with Et2O and water and the layers were separated. The Et2O layer was discarded. The aq. layer was acidified with 2 M HCl and extracted with EtOAc (3×). The combined EtOAc layers were dried over anhydrous Na2SO4, filtered and concentrated to give a light yellow solid. m/z (ESI, +ve) 498.2 (M+H)+. The light yellow solid was dissolved in 1 mL of dioxane and treated with 4.0 M HCl in 1,4-dioxane (Sigma-Aldrich) (5 mL, 20.00 mmol) at RT. After 24 h, the reaction mixture was concentrated and the orange solid was collected by filtration to give 2-(1-aminocyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (295c) (180 mg, 0.42 mmol, 95% yield). m/z (ESI, +ve) 381.1 (M−NH2)+.

후처리

  1. customA glass microwave reaction vessel
  2. temperatureAfter cooling to RT
  3. customthe layers were separated
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined EtOAc layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a light yellow solid
  9. concentrationthe reaction mixture was concentrated
  10. filtrationthe orange solid was collected by filtration

출처 및 근거

ORD 기록
ord-7afe19e5983742aeb1ccba963cc98680
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

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