Triethylamine → 2-(4-Bromo-2-fluoro-phenyl)-N-[3-(morpholine-4-carbonyl)-5-trifluoromethyl-phenyl]-acetamide

HRID 1446700노트

반응식

HRID 1446700 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([F:12])[CH:3]=1.Cl.CN(C)CCCN=C=NCC.[NH2:25][C:26]1[CH:27]=[C:28]([C:36]([N:38]2[CH2:43][CH2:42][O:41][CH2:40][CH2:39]2)=[O:37])[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1.CCN(CC)CC>C1COCC1.C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:25][C:26]2[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[C:28]([C:36]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[O:37])[CH:27]=2)=[O:11])=[C:4]([F:12])[CH:3]=1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acidHCID 66876746Morpholine, 4-[3-amino-5-(trifluoromethyl)benzoyl]-

생성물 1

HCID 685434652-(4-Bromo-2-fluoro-phenyl)-N-[3-(morpholine-4-carbonyl)-5-trifluoromethyl-phenyl]-acetamide수율 15%

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

Dissolve (4-bromo-2-fluoro-phenyl)-acetic acid (692 mg, 3.0 mmol) in THF (24 mL) and add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (618 mg, 3.2 mmol), stir for 10 minutes. Dissolve (3-amino-5-trifluoromethyl-phenyl)-morpholin-4-yl-methanone (740 mg, excluding excess ammonium chloride) from previous step in DCM (24 mL) with Et3N (3.3 mL, 23 mmol). Add the activated acid to the amine mixture and stir at room temperature for overnight. Dilute the resulting suspension with EtOAc and wash with saturated NaHCO3 and aqueous saturated sodium chloride successively. Dry the organic layer (MgSO4), concentrate and purify by silica gel column chromatography (EtOAc/Hexane gradient) to obtain the title compound (15% yield). LCMS (ES), m/z 491 (M+1).

후처리

  1. stirringstir at room temperature for overnight
  2. washwash with saturated NaHCO3 and aqueous saturated sodium chloride successively
  3. dry with materialDry the organic layer (MgSO4)
  4. concentrationconcentrate
  5. custompurify by silica gel column chromatography (EtOAc/Hexane gradient)

출처 및 근거

ORD 기록
ord-c5e2c30bf045471c93be85cef0b8f2b5
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07666879B2

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