Trifluoroacetic acid → HCID 59394094, compound

HRID 1887669Notes

Reaction equation

HRID 1887669 reaction equation
[CH:1]1([C:4]2[N:8]([CH2:9][CH3:10])[N:7]=[C:6]([NH:11][C:12]([N:14]3[C:22]4[C:17](=[CH:18][C:19]([O:23][C:24]5[CH:29]=[CH:28][N:27]=[C:26]([CH2:30][N:31](C)[C:32](=O)OC(C)(C)C)[N:25]=5)=[CH:20][CH:21]=4)[CH:16]=[CH:15]3)=[O:13])[CH:5]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1([C:4]2[N:8]([CH2:9][CH3:10])[N:7]=[C:6]([NH:11][C:12]([N:14]3[C:22]4[C:17](=[CH:18][C:19]([O:23][C:24]5[CH:29]=[CH:28][N:27]=[C:26]([CH2:30][NH:31][CH3:32])[N:25]=5)=[CH:20][CH:21]=4)[CH:16]=[CH:15]3)=[O:13])[CH:5]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59394726HCID 59394726, compound

Product 1

HCID 59394094HCID 59394094, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (4-(1-(5-cyclopropyl-1-ethyl-1H-pyrazol-3-ylcarbamoyl)-1H-indol-5-yloxy)pyrimidin-2-yl)methyl(methyl)carbamate (33 mg, 0.062 mmol) in DCM (2 mL) at 0° C. is added TFA (0.7 mL, 9.1 mmol). The reaction is stirred for 30 minutes at 0° C. and is then placed at room temperature for an additional 20 minutes. The reaction mixture is then concentrated in vacuo to near dryness and then diluted with DCM and water. The mixture is neutralized by the addition of saturated aqueous NaHCO3 and the resulting layers are separated. The aqueous layer is extracted two additional times with DCM. The organic layers are combined, dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue is purified via FCC (0-20% MeOH)/DCM) to give the title compound. MS (ESI) m/z 432.2 (M+1). (DMSO-d6) δ ppm 0.62-0.71 (m, 2H) 0.93-1.02 (m, 2H) 1.37 (t, J=7.20 Hz, 3H) 1.86-1.99 (m, 1H) 2.30 (s, 3H) 3.71 (s, 2H) 4.15 (q, J=7.24 Hz, 2H) 6.16 (s, 1H) 6.71 (d, J=4.29 Hz, 1H) 6.87 (d, J=5.56 Hz, 1H) 7.12 (dd, J=9.09, 2.27 Hz, 1H) 7.46 (d, J=2.27 Hz, 1H) 8.17 (d, J=3.79 Hz, 1H) 8.31 (d, J=9.09 Hz, 1H) 8.61 (d, J=5.56 Hz, 1H) 10.64 (s, 1H).

Workup

  1. waitis then placed at room temperature for an additional 20 minutes
  2. concentrationThe reaction mixture is then concentrated in vacuo
  3. additiondiluted with DCM and water
  4. additionThe mixture is neutralized by the addition of saturated aqueous NaHCO3
  5. customthe resulting layers are separated
  6. extractionThe aqueous layer is extracted two additional times with DCM
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue is purified via FCC (0-20% MeOH)/DCM)

Sources & evidence

ORD record
ord-5ae76dc9699c4d9cb9f5305763413def
Source dataset
uspto-grants-2013_08
Patent number
US08501756B2

Reaction notes

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