Trifluoroacetic acid → HCID 57418644, compound

HRID 2114385Notes

Reaction equation

HRID 2114385 reaction equation
[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.[CH2:23]([O:25][C:26]([C:28]1[CH:29]=[CH:30][C:31]2[O:36][CH2:35][C:34](=[O:37])[N:33]([CH2:38][C:39]([OH:41])=O)[C:32]=2[CH:42]=1)=[O:27])[CH3:24].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>C(Cl)Cl.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:39](=[O:41])[CH2:38][N:33]2[C:32]3[CH:42]=[C:28]([C:26]([O:25][CH2:23][CH3:24])=[O:27])[CH:29]=[CH:30][C:31]=3[O:36][CH2:35][C:34]2=[O:37])[CH2:8][N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57425536[1-(4-Biphenylyl)-2-(4-morpholinyl)ethyl]methylamineHCID 57457165HCID 57457165, compound

Product 1

HCID 57418644HCID 57418644, compoundYield 43.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

1-(4-biphenylyl)-N-methyl-2-(4-morpholinyl)ethanamine (0.68 g, 2.3 mmol) and {6-[(ethyloxy)carbonyl]-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl} acetic acid (0.8 g, 2.5 mmol) were dissolved in 12 mL of methylene chloride. Triethylamine (1.3 mL, 9.2 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, 1.11 g, 2.5 mmol) dissolved in 5 mL of methylene chloride 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=2.7 min and m/e 558 [M+1]+. Solvent was removed by rotary evaporation 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 (0.58 g. 1.0 mmol, 43%) as an off-white amorphous solid. MS (ES) m/e 558 [M+H]+.

Workup

  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. customSolvent was removed by rotary evaporation
  5. customthe crude residue was purified by prep HPLC (Waters, 50×100 mm, 84 mL/min

Sources & evidence

ORD record
ord-362637237a6f4c6c87979512f4350739
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

Loading…