Trifluoroacetic acid → HCID 71625975, compound

HRID 1396438Notes

Reaction equation

HRID 1396438 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]([CH2:34][CH2:35][CH3:36])[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]([CH2:34][CH2:35][CH3:36])[N:27]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689781HCID 86689781, compound

Product 1

HCID 71625975HCID 71625975, compoundYield 77.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (96 mg, 192 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (438 mg, 296 μL, 3.84 mmol) and the mixture stirred at room temperature overnight. The mixture was concentrated in vacuo then diluted with 25% aqueous NH4OH and dichloromethane. The phases were separated and the organic phase washed with water. The organic layer was concentrated in vacuo then purified by chromatography (silica, 3 to 20% methanol in dichloromethane) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(5-methoxy-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (59 mg, 148 μmol, 77%) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.36 (s, 1H), 8.30 (s, 1H), 7.72 (s, 1H), 7.60 (s, 1H), 7.42 (d, J=8.8 Hz, 1H), 6.87 (d, J=8.8 Hz, 1H), 6.72 (d, J=7.6 Hz, 1H), 3.96 (s, 1H), 3.79 (s, 3H), 3.28 (s, 1H), 2.72 (t, J=7.3 Hz, 2H), 1.54-1.74 (m, 8H), 1.35 (m, 2H), 0.94 (t, J=7.4 Hz, 3H); MS (EI/CI) m/z: 400.2 [M+H].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthen diluted with 25% aqueous NH4OH and dichloromethane
  3. customThe phases were separated
  4. washthe organic phase washed with water
  5. concentrationThe organic layer was concentrated in vacuo
  6. customthen purified by chromatography (silica, 3 to 20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a2b8ae4b17b1470795836987e6585d42
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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