Dimethylformamide → 3-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)propanamide TFA

HRID 1506461ノート

反応式

HRID 1506461 の反応式
Br[CH2:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[C:17]([C:18]([F:21])([F:20])[F:19])=[C:16]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[O:15][N:14]=3)=[C:8]1[CH2:7][CH2:6]2.[CH3:31][NH:32][CH2:33][CH2:34][C:35]([NH2:37])=[O:36].C(N(CC)CC)C.CN([CH:48]=[O:49])C>C(OCC)(=O)C>[OH:36][C:48]([C:18]([F:21])([F:20])[F:19])=[O:49].[CH3:31][N:32]([CH2:2][C:3]1[CH:4]=[C:5]2[C:28](=[CH:29][CH:30]=1)[C:9]1=[N:10][O:11][C:12]([C:13]3[C:17]([C:18]([F:21])([F:20])[F:19])=[C:16]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[O:15][N:14]=3)=[C:8]1[CH2:7][CH2:6]2)[CH2:33][CH2:34][C:35]([NH2:37])=[O:36]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 22182162N~3~-Methyl-beta-alaninamideHCID 671678437-(Bromomethyl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole

生成物 1

HCID 866699153-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)propanamide TFA収率 48%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 7-(bromomethyl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (6C, 0.025 g, 0.053 mmol), 3-(methylamino)propanamide (5.37 mg, 0.053 mmol) and triethylamine (7.33 mL, 0.053 mmol) in DMF (3.0 mL) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with water (3×1.0 mL). The ethyl acetate extract was concentrated, and the residue was chromatographed using reverse-phase preparative HPLC (Column: LUNA 5 u C18, 21×100 mm:Solvent MeOH(B)—H2O(A), 0.1% TFA: 0% B-100% B, Gradient Time 12 min, Stop Time 20 min, Flow Rate 20 ml/min, Wavelength 220 nM) to give 3-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)propanamide TFA (0.012 g., 0.493 mmol, 48%) as a viscous tan liquid. The product had an HPLC ret. time=4.02 min. (condition B). LC/MS M+1=497.07. 1H NMR (400 MHz, CD3OD) δ ppm 8.09 (1H, d, J=7.92 Hz), 7.79 (2H, d, J=7.26 Hz), 7.32-7.77 (5H, m), 4.54 (2H, s), 3.23-3.44 (4H, m), 2.98-3.21 (4H, m), and 2.89 (3H, s).

後処理

  1. washwashed with water (3×1.0 mL)
  2. extractionThe ethyl acetate extract
  3. concentrationwas concentrated
  4. customthe residue was chromatographed
  5. customreverse-phase preparative HPLC (Column: LUNA 5 u C18, 21×100 mm:Solvent MeOH(B)—H2O(A), 0.1% TFA: 0% B-100% B, Gradient Time 12 min, Stop Time 20 min, Flow Rate 20 ml/min, Wavelength 220 nM)

出典と根拠

ORDレコード
ord-908972ae395241c2824fe1f6af27442d
出典データセット
uspto-grants-2015_12
特許番号
US09216972B2

反応ノート

読み込み中…