Trifluoroacetic acid → N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-N-methyl-2-{3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetamide

HRID 2354394ノート

反応式

HRID 2354394 の反応式
[C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][C:4]([CH:7]([NH:15][CH3:16])[CH2:8][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:3][CH:2]=1.[O:23]=[C:24]1[N:29]([CH2:30][C:31]([OH:33])=O)[C:28]2[CH:34]=[C:35]([O:38][C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:37][C:27]=2[O:26][CH2:25]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.FC(F)(F)C(O)=O>CN(C)C=O.CC#N.O>[C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:2]=[CH:3][C:4]([CH:7]([N:15]([CH3:16])[C:31](=[O:33])[CH2:30][N:29]2[C:28]3[CH:34]=[C:35]([O:38][C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:37][C:27]=3[O:26][CH2:25][C:24]2=[O:23])[CH2:8][N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)=[CH:5][CH:6]=1

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57425536[1-(4-Biphenylyl)-2-(4-morpholinyl)ethyl]methylamineHCID 57488862{3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl}acetic acid

生成物 1

HCID 57418647N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-N-methyl-2-{3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetamide収率 47.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]methylamine (0.1 g, 0.34 mmol) and {3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl}acetic acid (0.108 g, 0.37 mmol) were dissolved in 1 mL of dimethylformamide. Triethylamine (0.13 mL, 0.93 mmol) was delivered to the room temperature mixture, and the solution was allowed to stir for several minutes before a separate solution of 1H-1,2,3-benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 0.164 g, 0.37 mmol) dissolved in 1 mL of dimethylformamide was added to the mixture at room temperature. The reaction was maintained at that temperature for 18 hours, before it was determined to be complete by LCMS (two Aquasil C18, 20×1 mm columns were run in sequence, 4 minutes at 0.1 mL/min, 1-99% CH3CN/H2O with 0.018% trifluoroacetic acid, ES) Rt=2.52 min and m/e 570 [M+1]+. The reaction mixture was filtered through a 0.45 μm PTFE Acrodisk and the crude residue was purified by prep HPLC (Waters, 50×100 mm, 84 mL/min, A: acetonitrile B: water (pH=10, NH4OH), A: 10 to 99% over 15 min, UV detection at 214 nm) to give the title compound (0.089 g. 0.16 mmol, 42%) as an off-white amorphous solid. MS (ES) m/e 570 [M+H]+.

後処理

  1. customwas delivered to the room temperature mixture
  2. additionwas added to the mixture at room temperature
  3. temperatureThe reaction was maintained at that temperature for 18 hours, before it
  4. filtrationThe reaction mixture was filtered through a 0.45 μm PTFE Acrodisk
  5. customthe crude residue was purified by prep HPLC (Waters, 50×100 mm, 84 mL/min

出典と根拠

ORDレコード
ord-f96e84c01a2545e985fdc941d3c6fa6e
出典データセット
uspto-grants-2010_07
特許番号
US07749998B2

反応ノート

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