Diisopropylethylamine → N-(2-amino-4-chloro-5-(trifluoromethyl)phenyl)-3-(3-oxocyclobutyl)propanamide

HRID 511604

반응식

HRID 511604 반응식
[O:1]=[C:2]1[CH2:5][CH:4]([CH2:6][CH2:7][C:8]([OH:10])=O)[CH2:3]1.[Cl:11][C:12]1[CH:13]=[C:14]([NH2:23])[C:15]([NH2:22])=[CH:16][C:17]=1[C:18]([F:21])([F:20])[F:19].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>CN(C)C=O>[NH2:23][C:14]1[CH:13]=[C:12]([Cl:11])[C:17]([C:18]([F:21])([F:19])[F:20])=[CH:16][C:15]=1[NH:22][C:8](=[O:10])[CH2:7][CH2:6][CH:4]1[CH2:3][C:2](=[O:1])[CH2:5]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 27734974-Chloro-5-(trifluoromethyl)benzene-1,2-diamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 677753573-(3-Oxocyclobutyl)propanoic acid

생성물 1

HCID 67773908N-(2-amino-4-chloro-5-(trifluoromethyl)phenyl)-3-(3-oxocyclobutyl)propanamide수율 31%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 3-(3-oxocyclobutyl)propanoic acid (157 mg, 0.696 mmol) and 4-chloro-5-(trifluoromethyl)benzene-1,2-diamine (146 mg, 0.696 mmol) in N,N-dimethylformamide (2.5 mL) was cooled at 0° C. The solution was treated with N,N-diisopropylethylamine (0.364 mL, 2.09 mmol) dropwise followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (291 mg, 0.765 mmol) in one portion. The solution was allowed to stir and slowly wane to room temperature. After 40 h, the reaction mixture was concentrated partially under high vac. The remaining brown liquid was taken up in 25 mL EA and 15 mL 1/1 sat NaHCO3/H2O and extracted. The aqueous phase was washed with two 15 mL portions of ethyl acetate and the combined organic phase was washed with 30 mL portions of H2O and brine. The organic phase was dried over MgSO4, filtered and concentrated to yield a tannish brown viscous oil/glass. The crude material was purified by flash chromatography (40 g silica gel, 50-80% EA/hept) to yield the title compound (72 mg, 31%) as a slightly tan glass/stiff foam: MS (ESI+) for C14H14ClF3N2O2 m/z 335.2 (M+H)+; MS (ESI−) for C14H14ClF3N2O2 m/z 333.3 (M−H)−; HPLC purity 78.2% (ret. time, 3.56 min).

후처리

  1. customslowly wane to room temperature
  2. concentrationthe reaction mixture was concentrated partially under high vac
  3. extractionextracted
  4. washThe aqueous phase was washed with two 15 mL portions of ethyl acetate
  5. washthe combined organic phase was washed with 30 mL portions of H2O and brine
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a tannish brown viscous oil/glass
  10. customThe crude material was purified by flash chromatography (40 g silica gel, 50-80% EA/hept)

출처 및 근거

ORD 기록
ord-9fd74dff54dd409da9ebf1211ca08921
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096634B2

연결된 노트

불러오는 중…