Dimethylformamide → HCID 89543886, compound

HRID 922788Notes

Reaction equation

HRID 922788 reaction equation
[NH2:1][C:2]([C:4]1[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:11]2[C:6](=[CH:7][C:8]([C:21]([OH:23])=O)=[CH:9][CH:10]=2)[N:5]=1)=[O:3].[NH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN(C=O)C>C(Cl)Cl>[F:20][C:17]1[CH:16]=[CH:15][C:14]([C:12]2[C:11]3[C:6](=[CH:7][C:8]([C:21]([N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[O:23])=[CH:9][CH:10]=3)[N:5]=[C:4]([C:2]([NH2:1])=[O:3])[CH:13]=2)=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 31268PyrrolidineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 89543691HCID 89543691, compound

Product 1

HCID 89543886HCID 89543886, compoundYield 85.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(Aminocarbonyl)-4-(4-fluorophenyl)quinoline-7-carboxylic acid (5-3, 50.0 mg, 0.161 mmol, 1.0 equiv), pyrrolidine (11.5 mg, 0.161 mmol, 1.0 equiv.), BOP (93.0 mg, 0.209 mmol, 1.3 equiv.), and TEA (0.0670 mL, 0.483 mmol, 3 equiv) were dissolved into DMF (1.0 mL) and stirred at room temperature for 1 hour. The mixture was diluted with methylene chloride, washed with water, brine, dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 4-(4-Fluorophenyl)-7-(pyrrolidin-1-ylcarbonyl)quinoline-2-carboxamide (5-4, 50.0 mg, 85.0%) as a colorless solid. 1H NMR (500 MHz, CDCl3): δ 8.324 (d, J=1.47 Hz, 1H); 8.273 (s, 1H); 8.251 (br s, 1H); 8.026 (d, J=8.78 Hz, 1H); 7.762 (dd, J1=8.54 Hz, J2=1.71 Hz, 1H); 7.501-7.529 (m, 2H); 7.246-7.286 (m, 2H); 6.750 (br s, 1H); 3.765 (tr, J=6.95 Hz, 2H); 3.567 (tr, J=6.68 Hz, 2H); 2.055 (quint, J=6.78 Hz, 2H); 1.962 (quint, J=6.65 Hz, 2H). LRMS m/z (M+H)+ 364.1 found, 364.1 required.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)

Sources & evidence

ORD record
ord-472cb1f0892e4d0e8446043824d7329a
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

Loading…