Trifluoroacetic acid → HCID 71626043, compound

HRID 1396450Notes

Reaction equation

HRID 1396450 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]([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[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]([CH:34]([CH3:36])[CH3:35])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689789HCID 86689789, compound

Product 1

HCID 71626043HCID 71626043, compoundYield 74.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (86 mg, 171 μmol) in dichloromethane (2.7 mL) was added trifluoroacetic acid (391 mg, 264 μL, 3.43 mmol) and stirred at room temperature for 16 h. The reaction mixture was then diluted with dichloromethane, concentrated in vacuo, and purified by chromatography (silica, 0 to 12% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (51 mg, 127 μmol, 74%) as a yellow solid. 1H NMR (400 MHz, METHANOL-d6) δ ppm 8.08 (s, 1H), 7.42 (d, J=8.6 Hz, 1H), 6.91 (d, J=8.9 Hz, 1H), 4.35 (m, 1H), 4.12 (dd, J=12.1, 3.4 Hz, 1H), 4.07 (d, J=12.6 Hz, 1H), 3.89 (s, 1H), 3.88 (s, 3H), 3.80 (d, J=12.8 Hz, 1H), 3.65 (m, 1H), 3.52 (m, 1H), 2.12 (m, 1H), 1.96 (d, J=13.1 Hz, 1H), 1.32 (d, J=5.8 Hz, 6H); MS (EI/CI) m/z: 402.3 [M+H].

Workup

  1. concentrationconcentrated in vacuo
  2. custompurified by chromatography (silica, 0 to 12% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane)

Sources & evidence

ORD record
ord-19e39b7eaac3481688d3fa4d27c8c4cc
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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