Trifluoroacetic acid → HCID 71626044, compound

HRID 1396454Notes

Reaction equation

HRID 1396454 reaction equation
[C:1]([C:4]1[N:9]=[N:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17]C(=O)OC(C)(C)C)=[CH:6][C:5]=1[NH:25][C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH:33]([CH3:35])[CH3:34])[N:27]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl>[NH2:17][C@H:12]1[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]1[NH:10][C:7]1[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH:33]([CH3:35])[CH3:34])[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689792HCID 86689792, compound

Product 1

HCID 71626044HCID 71626044, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-isopropyl-4-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (35 mg, 72.4 μmol) in dichloromethane (1.1 mL) was added trifluoroacetic acid (165 mg, 112 μL, 1.45 mmol) and the mixture stirred at room temperature for 20 h. The mixture was concentrated in vacuo and then the residue diluted with dichloromethane and a few drops of 25% aqueous NH4OH added until the mixture was measured at pH˜8. The mixture was then washed with water, the organic phase collected, concentrated in vacuo, and finally purified by chromatography (silica, 3 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-isopropyl-4-methylpyridin-2-ylamino)pyridazine-3-carboxamide (15 mg, 39.1 μmol, 54%) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.64 (s, 1H), 8.36 (s, 1H), 8.07 (s, 1H), 7.64 (s, 1H), 6.79 (d, J=4.3 Hz, 1H), 6.73 (s, 1H), 6.60 (s, 1H), 3.90 (s, 1H), 2.98 (m, 1H), 2.27 (s, 3H), 1.52-1.76 (m, 6H), 1.38 (m, 2H), 1.27 (d, J=7.0 Hz, 6H); MS (EI/CI) m/z: 384.1 [M+H].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue diluted with dichloromethane and a few drops of 25% aqueous NH4OH
  3. additionadded until the mixture
  4. washThe mixture was then washed with water
  5. customthe organic phase collected
  6. concentrationconcentrated in vacuo
  7. customfinally purified by chromatography (silica, 3 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane)

Sources & evidence

ORD record
ord-a15a01897aa94791acaa001322d52a2f
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

Loading…