Trifluoroacetic acid → HCID 71626041, compound

HRID 1396443Notes

Reaction equation

HRID 1396443 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]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([CH:34]([CH3:36])[CH3:35])[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]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([CH:34]([CH3:36])[CH3:35])[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689785HCID 86689785, compound

Product 1

HCID 71626041HCID 71626041, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (100 mg, 200 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (456 mg, 308 μL, 4.00 mmol) and the mixture stirred at room temperature for 16 h. The mixture was concentrated in vacuo then 25% aqueous NH4OH solution added. This was then diluted with dichloromethane and water, the phases separated, and the organic phase washed twice with water. The organic layer was dried over anhydrous magnesium sulfate then purified by chromatography (silica, 0 to 15% methanol in dichloromethane) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (43 mg, 108 μmol, 54%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.45 (s, 1H), 8.31 (s, 1H), 7.69 (s, 1H), 7.58 (s, 1H), 7.42 (d, J=8.7 Hz, 1H), 6.85 (d, J=8.7 Hz, 1H), 6.63 (d, J=8.0 Hz, 1H), 3.80 (s, 3H), 3.42 (m, 1H), 3.15 (s, 1H), 1.52-1.69 (m, 8H), 1.32 (m, 2H), 1.24 (d, J=6.4 Hz, 6H); MS (EI/CI) m/z: 400.3 [M+H].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. addition25% aqueous NH4OH solution added
  3. additionThis was then diluted with dichloromethane and water
  4. customthe phases separated
  5. washthe organic phase washed twice with water
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. customthen purified by chromatography (silica, 0 to 15% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9c44bc80035e4b009b14428734b82f94
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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