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

HRID 38756

反応式

HRID 38756 の反応式
[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]

参加物

5

反応物 2

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

生成物 1

HCID 70678916N-Desmethylenzalutamide

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-5e358dae823b4bd29d7a4dcebbbfc529
出典データセット
uspto-grants-2013_09
特許番号
US08524755B2

関連ノート

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