Trifluoroacetic acid → HCID 57418648, compound

HRID 2354399Notes

Reaction equation

HRID 2354399 reaction equation
[C:1]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:6]=[CH:5][C:4]([CH:7]([NH:14][CH3:15])[CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:3][CH:2]=1.[CH3:22][O:23][C:24]1[C:38]([C:39]([F:42])([F:41])[F:40])=[CH:37][C:27]2[N:28]([CH2:33][C:34]([OH:36])=O)[C:29](=[O:32])[CH2:30][O:31][C:26]=2[CH: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:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:6]=[CH:5][C:4]([CH:7]([N:14]([CH3:15])[C:34](=[O:36])[CH2:33][N:28]2[C:27]3[CH:37]=[C:38]([C:39]([F:42])([F:41])[F:40])[C:24]([O:23][CH3:22])=[CH:25][C:26]=3[O:31][CH2:30][C:29]2=[O:32])[CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:3][CH:2]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27567161-([1,1'-Biphenyl]-4-yl)-N-methyl-2-(pyrrolidin-1-yl)ethan-1-amineHCID 57457166HCID 57457166, compound

Product 1

HCID 57418648HCID 57418648, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]methylamine (0.084 g, 0.30 mmol) and [7-(methyloxy)-3-oxo-6-(trifluoromethyl)-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetic acid (0.1 g, 0.33 mmol) were dissolved in 1 mL of dimethylformamide. Triethylamine (0.13 mL, 0.9 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, 0.146 g, 0.33 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=2.1 min and m/e 568 [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 (0.070 g. 0.12 mmol, 41%) as an off-white amorphous solid. MS (ES) m/e 568 [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. 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

Sources & evidence

ORD record
ord-f8ead9528b81416f9f16592ebbd93aea
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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