Trifluoroacetic acid → 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide

HRID 1396474Notes

Reaction equation

HRID 1396474 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]=[C:30]([CH3:32])[CH:29]=[C:28]([CH2:33][CH2:34][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]=[C:30]([CH3:32])[CH:29]=[C:28]([CH2:33][CH2:34][CH3:35])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689803tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

Product 1

HCID 716261006-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamideYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (27 mg, 55.6 μmol) in dichloromethane (1 mL) was added trifluoroacetic acid (127 mg, 85.7 μL, 1.11 mmol) and the mixture stirred at room temperature for 16 h. The mixture was concentrated in vacuo and then the residue was diluted with dichloromethane and 25% aqueous NH4OH. The mixture was washed with water (2×), then the organic phase was collected, concentrated in vacuo, and purified by chromatography (silica, 1 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (7 mg, 18.2 μmol, 33%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.61 (s, 1H), 8.38 (s, 1H), 8.10 (s, 1H), 7.68 (s, 1H), 6.98 (d, J=5.8 Hz, 1H), 6.71 (s, 1H), 6.61 (s, 1H), 4.08 (q, J=5.5 Hz, 1H), 3.92 (d, J=9.9 Hz, 1H), 3.81 (d, J=12.2 Hz, 1H), 3.59 (d, J=11.7 Hz, 1H), 3.47 (t, J=11.8 Hz, 1H), 3.28 (s, 1H), 3.17 (d, J=5.0 Hz, 2H), 2.67 (t, J=7.8 Hz, 1H), 2.33 (s, 1H), 2.26 (s, 3H), 1.72 (m, 3H), 1.23 (s, 1H), 0.93 (t, J=7.4 Hz, 3H); MS (EI/CI) m/z: 386.2 [M+H].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue was diluted with dichloromethane and 25% aqueous NH4OH
  3. washThe mixture was washed with water (2×)
  4. customthe organic phase was collected
  5. concentrationconcentrated in vacuo
  6. custompurified by chromatography (silica, 1 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane)

Sources & evidence

ORD record
ord-4ee0cc7532e9421a80a7fc4778dd346e
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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