tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate → HCID 86689814, compound

HRID 1396489Notes

Reaction equation

HRID 1396489 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[C:14]([O:21][CH3:22])[N:13]=2)[CH:3]=1.[NH2:23][C@@H:24]1[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]>CN1C(=O)CCC1.C(OCC)(=O)C.[Cl-].[Na+].O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:23][C@@H:24]2[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[C:14]([O:21][CH3:22])[N:13]=1)(=[O:9])[NH2:10]

Participants

6

Reactant 2

HCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamateHCID 86689813HCID 86689813, compound

Product 1

HCID 86689814HCID 86689814, compoundYield 36.2%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 6-chloro-4-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (250 mg, 777 μmol) in NMP (2.6 mL) was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (672 mg, 2.33 mmol) in four portions approximately every 12 h and heated to 140° C. in the periods between additions. After a total of 48 h, the mixture was cooled then diluted with ethyl acetate and brine. The phases were separated then the organic phase was washed with brine (2×), concentrated in vacuo and purified by chromatography (silica, 0 to 4% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane) to give 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, 36%) as light brown solid. MS (EI/CI) m/z: 502.3 [M+H].

Workup

  1. temperatureAfter a total of 48 h, the mixture was cooled
  2. customThe phases were separated
  3. washthe organic phase was washed with brine (2×)
  4. concentrationconcentrated in vacuo
  5. custompurified by chromatography (silica, 0 to 4% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane)

Sources & evidence

ORD record
ord-28bd13354e534d348d0c3dbbcc110170
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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