Trifluoroacetic acid → HCID 71626103, compound

HRID 1396490Notes

Reaction equation

HRID 1396490 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]([CH:32]([CH3:34])[CH3:33])=[C:28]([O:35][CH3:36])[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][C:29]([CH:32]([CH3:34])[CH3:33])=[C:28]([O:35][CH3:36])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689814HCID 86689814, compound

Product 1

HCID 71626103HCID 71626103, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (141 mg, 281 μmol) in dichloromethane (4.3 mL) was added trifluoroacetic acid (641 mg, 433 μL, 5.62 mmol) and the mixture stirred at room temperature 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-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (35 mg, 87 μmol, 31%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.53 (s, 1H), 8.37 (s, 1H), 7.70 (s, 1H), 7.62 (s, 1H), 7.54 (d, J=8.1 Hz, 1H), 6.80 (d, J=7.8 Hz, 1H), 6.54 (d, J=8.0 Hz, 1H), 4.05 (br. s, 1H), 3.81 (d, J=11.9 Hz, 1H), 3.67 (dd, J=10.9, 3.5 Hz, 1H), 3.49 (dd, J=11.1. 1.9 Hz, 1H), 3.37 (m, 2H), 3.08 (m, 1H), 2.97 (s, 1H), 1.81 (m, 1H), 1.65 (m, 1H), 1.16 (d, J=6.8 Hz, 6H); MS (EI/CI) m/z: 402.3 [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-ef16cba9147740dda9ca454f0513a46b
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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