tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate → tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

HRID 1396473Notes

Reaction equation

HRID 1396473 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]=[C:16]([CH3:18])[CH:15]=[C:14]([CH2:19][CH2:20][CH3:21])[N:13]=2)[CH:3]=1.[NH2:22][C@@H:23]1[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33]>CN1C(=O)CCC1.C(OCC)(=O)C.[Cl-].[Na+].O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:22][C@@H:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH2:19][CH2:20][CH3:21])[N:13]=1)(=[O:9])[NH2:10]

Participants

6

Reactant 2

HCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamateHCID 86689801HCID 86689801, compound

Product 1

HCID 86689803tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamateYield 23.4%

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-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (73 mg, 239 μmol, prepared as described in example 38) in NMP (796 μL) was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (206.4 mg, 956 μmol) in 4 portions approximately every 12 h over 48 h and heated at 140° C. in the periods between additions. After 48 h, the mixture was diluted with ethyl acetate and brine. The phases were separated then the organic phase was washed with brine (3×), concentrated in vacuo, and purified by chromatography (silica, 1 to 5% methanol in dichloromethane) to give tert-butyl (3R,4R)-4-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (27 mg, 56 μmol, 23%) as a light brown solid. MS (EI/CI) m/z: 486.2 [M+H].

Workup

  1. customThe phases were separated
  2. washthe organic phase was washed with brine (3×)
  3. concentrationconcentrated in vacuo
  4. custompurified by chromatography (silica, 1 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-6975d9bad6554cc9b1b9df67dcf5bf2f
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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