4-Isothiocyanato-2-(trifluoromethyl)benzonitrile → N-Desmethylenzalutamide

HRID 38756

반응식

HRID 38756 반응식
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([CH3:17])([CH3:16])[C:12]([O:14]C)=O)=[CH:6][C:5]=1[F:18])(=[O:3])[NH2:2].[F:19][C:20]([F:33])([F:32])[C:21]1[CH:28]=[C:27]([N:29]=[C:30]=[S:31])[CH:26]=[CH:25][C:22]=1[C:23]#[N:24]>CS(C)=O.O>[C:23]([C:22]1[CH:25]=[CH:26][C:27]([N:29]2[C:12](=[O:14])[C:11]([CH3:17])([CH3:16])[N:10]([C:7]3[CH:8]=[CH:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([F:18])[CH:6]=3)[C:30]2=[S:31])=[CH:28][C:21]=1[C:20]([F:19])([F:32])[F:33])#[N:24]

참가 물질

5

반응물 2

HCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 66617687Alanine, N-[4-(aminocarbonyl)-3-fluorophenyl]-2-methyl-, methyl ester

생성물 1

HCID 70678916N-Desmethylenzalutamide

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

실험 절차

A solution of methyl 2-(4-carbamoyl-3-fluorophenylamino)-2-methylpropanoate and 2-(trifluoromethyl)-4-isothiocyanatobenzonitrile (1.5 equivalents) in dry DMSO (5 mL per mmol) was heated to 80-82° C. for 12 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 40% Acetone-Hexanes. MS (m/z): 451 (M+1). HPLC: Column, YMC ODS A, 4.6×150 mm, 5 μm, Mobile Phase A:10 mM Ammonium acetate, Mobile Phase B: Acetonitrile, Gradient, 10% B up to 2 min, 10% to 90% B in 3 min, hold for 3 min, 90% to 10% B in 5 min, Retention time, 2.782 min, HPLC Purity, 99.4%, Flow Rate, 1 mL/min. 1H NMR (CDCl3, Freebase): δ (ppm) 8.3 (t, 1H), 8.0 (d, 1H) 7.98 (s, 1H), 7.8 (d, 1H), 7.27 (d, 1H), 7.2 (d, 1H), 6.65 (d, 1H), 6.0 (s, 1H), 1.62 (s,6H).

후처리

  1. extractionextracted with ethyl acetate
  2. concentrationThe combined organic layer was concentrated under reduced pressure
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with 40% Acetone-Hexanes
  5. wait10% to 90% B in 3 min
  6. waithold for 3 min
  7. wait90% to 10% B in 5 min
  8. customRetention time, 2.782 min, HPLC Purity, 99.4%, Flow Rate, 1 mL/min

출처 및 근거

ORD 기록
ord-5e358dae823b4bd29d7a4dcebbbfc529
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524755B2

연결된 노트

불러오는 중…