Trifluoroacetic acid → HCID 71626101, compound

HRID 1396476Notes

Reaction equation

HRID 1396476 reaction equation
[C:1]([C:4]1[N:9]=[N:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][O: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[C@H:11]([NH:10][C:7]2[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[C:28]([CH2:34][CH2:35][CH3:36])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689804HCID 86689804, compound

Product 1

HCID 71626101HCID 71626101, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (77 mg, 154 μmol) in dichloromethane (2.4 mL) was added trifluoroacetic acid (350 mg, 237 μL, 3.07 mmol) and the mixture stirred at room temperature. After 16 h the mixture was concentrated in vacuo then diluted with 25% aqueous NH4OH and dichloromethane. The mixture was washed with water, then the organic phase was concentrated in vacuo and purified by chromatography (silica, 3 to 10% methanol in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-methoxy-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (33 mg, 82.2 μmol, 54%) as a an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.37 (s, 1H), 8.33 (s, 1H), 7.74 (s, 1H), 7.58 (s, 1H), 7.41 (d, J=8.7 Hz, 1H), 6.87 (d, J=8.8 Hz, 1H), 6.76 (d, J=7.6 Hz, 1H), 3.98 (br. s, 1H), 3.84 (m, 1H), 3.79 (s, 3H), 3.70 (d, J=11.3 Hz, 1H), 3.51 (d, J=11.5 Hz, 1H), 3.40 (t, J=11.2 Hz, 1H), 2.99 (s, 1H), 2.72 (t, J=7.4 Hz, 2H), 1.81 (m, 1H), 1.72 (m, 2H), 1.72 (m, 3H), 0.94 (t, J=7.3 Hz, 3H); MS (EI/CI) m/z: 402.2 [M+H].

Workup

  1. concentrationAfter 16 h the mixture was concentrated in vacuo
  2. additionthen diluted with 25% aqueous NH4OH and dichloromethane
  3. washThe mixture was washed with water
  4. concentrationthe organic phase was concentrated in vacuo
  5. custompurified by chromatography (silica, 3 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-70cdea4ae04b4ccfa2cf07c10d7d36c7
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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