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 2354394노트

반응식

HRID 2354394 반응식
[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

참가 물질

8

반응물 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

생성물 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]acetamide수율 47.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 18373917Acetonitrile--water (1/1)용매

실험 절차

[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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-f96e84c01a2545e985fdc941d3c6fa6e
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07749998B2

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