Trifluoroacetic acid → HCID 57488843, compound

HRID 2114408Notes

Reaction equation

HRID 2114408 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.[O:22]=[C:23]1[N:27]([CH2:28][C:29]([OH:31])=O)[C:26]2[CH:32]=[C:33]([O:36][C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:35][C:25]=2[O:24]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:29](=[O:31])[CH2:28][N:27]2[C:26]3[CH:32]=[C:33]([O:36][C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:35][C:25]=3[O:24][C:23]2=[O:22])[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 57488865HCID 57488865, compound

Product 1

HCID 57488843HCID 57488843, compoundYield 6.3%

Reagents, catalysts & solvents 2

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

Procedure

[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]methylamine (0.09 g, 0.32 mmol) and [2-oxo-5-[(trifluoromethyl)oxy]-1,3-benzoxazol-3(2H)-yl]acetic acid (0.097 g, 0.35 mmol) were dissolved in 1 mL of dimethylformamide. Triethylamine (0.13 mL, 0.96 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, 0.155 g, 0.32 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=2.0 min and m/e 541 [M+1]+. The reaction mixture was filtered through a 0.45 μm PTFE Acrodisk and the crude residue was purified by prep HPLC (Waters, 30×75 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 (0.011 g. 0.02 mmol, 6%) as an off-white amorphous solid. MS (ES) m/e 541 [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, 30×75 mm, 84 mL/min

Sources & evidence

ORD record
ord-7e67934b06f34b91a4114856ca6acbd6
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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