Trifluoroacetic acid → HCID 71625973, compound

HRID 1396423Notes

Reaction equation

HRID 1396423 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]([CH3:33])[CH: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]([CH3:33])[CH:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689771tert-butyl (1S,2R)-2-(6-carbamoyl-5-(3,5-dimethylphenylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Product 1

HCID 71625973HCID 71625973, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(3,5-dimethylphenylamino)pyridazin-3-ylamino)cyclohexylcarbamate (30 mg, 66.0 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (151 mg, 102 μL, 1.32 mmol) and the mixture stirred at room temperature for 16 h. The mixture was concentrated in vacuo then diluted with dichloromethane and drops of 25% NH4OH added until the pH was measured to be ˜8. The weakly basic solution was washed with water, then the organic phase was concentrated in vacuo and purified by chromatography (silica, 30 to 100% of a 10:89.5:0.5 MeOH:dichloromethane:NH4OH solution in dichloromethane) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(3,5-dimethylphenylamino)pyridazine-3-carboxamide (17 mg, 48.0 mmol, 73%) as a light brown solid. 1H NMR (400 MHz, METHANOL-d6) δ0 ppm 6.90 (s, 2H), 6.88 (s, 1H), 6.50 (s, 1H), 4.32 (s, 1H), 1.63-1.84 (m, 6H), 1.51 (m, 2H); MS (EI/CI) m/z: 355.1 [M+H].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthen diluted with dichloromethane and drops of 25% NH4OH
  3. additionadded until the pH
  4. washThe weakly basic solution was washed with water
  5. concentrationthe organic phase was concentrated in vacuo
  6. custompurified by chromatography (silica, 30 to 100% of a 10:89.5:0.5 MeOH:dichloromethane:NH4OH solution in dichloromethane)

Sources & evidence

ORD record
ord-733b94993633491fb36fe9df9992ffe6
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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