Trifluoroacetic acid → HCID 67994756, compound

HRID 2361289Notes

Reaction equation

HRID 2361289 reaction equation
[C:1]([C:4]1[C:9]2[NH:10][C:11]3[C:16]([C:8]=2[C:7]([C:22]2[C:23]([CH3:40])=[C:24]([NH:28][CH2:29][C:30]4[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:31]=4[C:32]([OH:34])=O)[CH:25]=[CH:26][CH:27]=2)=[CH:6][N:5]=1)=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][O:20][CH3:21])[CH:12]=3)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O.C(NC(C)C)(C)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.CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[F:39][C:36]1[CH:35]=[C:31]2[C:30]([CH2:29][N:28]([C:24]3[C:23]([CH3:40])=[C:22]([C:7]4[C:8]5[C:16]6[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:14][CH:15]=6)[NH:10][C:9]=5[C:4]([C:1]([NH2:2])=[O:3])=[N:5][CH:6]=4)[CH:27]=[CH:26][CH:25]=3)[C:32]2=[O:34])=[CH:38][CH:37]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7912DiisopropylamineHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 679948572-((3-(1-Carbamoyl-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-fluorobenzoic acid

Product 1

HCID 67994756HCID 67994756, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of 2-((3-(1-carbamoyl-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-fluorobenzoic acid, TFA (31.6 mg, 0.048 mmol), N,N-diisopropylamine (0.013 mL, 0.072 mmol), BOP (27.7 mg, 0.063 mmol), and N-methylmorpholine (0.021 mL, 0.188 mmol) in DMF (4 mL) was heated at 45° C. for 1 hr. The mixture was diluted with ethyl acetate (60 mL), washed sequentially with water (3×25 mL) and brine (25 mL), and dried over anhydrous MgSO4. After the solvent was removed under vacuum, the residue was purified by reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (13.3 mg, 0.025 mmol, 51.0% yield) as a yellow solid. LCMS (M+H)+=525.09. 1H NMR (500 MHz, DMSO-d6) δ: 11.72 (s, 1H), 8.37 (s, 1H), 8.25 (s, 1H), 7.82-7.79 (m, 2H), 7.72 (d, J=7.8 Hz, 1H), 7.65 (m, 1H), 7.63-7.58 (m, 2H), 7.50 (d, J=6.9 Hz, 1H), 7.41 (d, J=2.2 Hz, 1H), 7.20 (d, J=8.6 Hz, 1H), 6.76 (dd, J1=8.9 Hz, J2=2.2 Hz, 1H), 5.08 (d, J=17.2 Hz, 1H), 4.98 (d, J=17.2 Hz, 1H), 4.21 (m, 2H), 3.77 (m, 2H), 3.40 (s, 3H), 1.92 (s, 3H).

Workup

  1. washwashed sequentially with water (3×25 mL) and brine (25 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. customAfter the solvent was removed under vacuum
  4. customthe residue was purified by reverse phase HPLC
  5. concentrationThe correct fraction was concentrated under vacuum
  6. extractionextracted with ethyl acetate (3×30 mL)
  7. extractionThe combined extract
  8. washwas washed with brine (30 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. customRemoval of solvent under vacuum

Sources & evidence

ORD record
ord-423ef168cc374be3bb427cb46d2e9fdc
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…