Trifluoroacetic acid → HCID 71626104, compound

HRID 1396493Notes

Reaction equation

HRID 1396493 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][CH:29]=[C:28]([O:32][CH:33]([CH3:35])[CH3:34])[N:27]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl.[NH4+].[OH-].O>[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][CH:29]=[C:28]([O:32][CH:33]([CH3:35])[CH3:34])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689817HCID 86689817, compound

Product 1

HCID 71626104HCID 71626104, compoundYield 46.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(6-isopropoxypyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (185 mg, 379 μmol) in dichloromethane (5.9 mL) was added trifluoroacetic acid (865 mg, 585 μL, 7.59 mmol) and the mixture stirred at r.t. for 16 h. The mixture was diluted with 25% aqueous NH4OH, dichloromethane, and water. The organic phase was separated and washed with water (2×), then concentrated in vacuo and purified by chromatography (silica, 3 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-(6-isopropoxypyridin-2-ylamino)pyridazine-3-carboxamide (68 mg, 176 μmol, 46%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.56 (s, 1H), 8.38 (s, 1H), 7.62 (m, 3H), 6.76 (d, J=7.7 Hz, 1H), 6.54 (d, J=7.8 Hz, 1H), 6.35 (d, J=8.2 Hz, 1H), 5.18 (m, 1H), 4.07 (br. s, 1H), 3.80 (d, J=11.3 Hz, 1H), 3.67 (dd, J=11.6, 3.8 Hz, 1H), 3.50 (dd, J=11.9. 2.3 Hz, 1H), 3.39 (m, 2H), 2.96 (s, 1H), 1.78 (m, 1H), 1.68 (m, 2H), 1.33 (dd, J=6.3, 1.7 Hz, 6H); MS (EI/CI) m/z: 388.3 [M+H].

Workup

  1. customThe organic phase was separated
  2. washwashed with water (2×)
  3. concentrationconcentrated in vacuo
  4. custompurified by chromatography (silica, 3 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane)

Sources & evidence

ORD record
ord-ea23aaa99897423dbb5d61647d617cb7
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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