tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate → HCID 86689804, compound

HRID 1396475Notes

Reaction equation

HRID 1396475 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]([O:18][CH3:19])=[C:14]([CH2:20][CH2:21][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]([O:18][CH3:19])=[C:14]([CH2:20][CH2:21][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 86689780HCID 86689780, compound

Product 1

HCID 86689804HCID 86689804, compoundYield 25%

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-methoxy-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (200 mg, 622 μmol, prepared as described in example 31) in NMP (2.1 mL) was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (402 mg, 1.86 mmol) in 3 portions approximately every 12 h and heated to 140° C. in the periods between additions. After a total of 36 h, the mixture was cooled, diluted with ethyl acetate and brine, then the organic phase separated and washed with brine (3×). The organic phase was then concentrated in vacuo and the residue obtained was purified by chromatography (silica, 1 to 5% methanol in dichloromethane) to give tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-methoxy-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (77 mg, 154 μmol, 25%) as a light brown solid. MS (EI/CI) m/z: 502.2 [M+H].

Workup

  1. temperatureAfter a total of 36 h, the mixture was cooled
  2. customthe organic phase separated
  3. washwashed with brine (3×)
  4. concentrationThe organic phase was then concentrated in vacuo
  5. customthe residue obtained
  6. customwas purified by chromatography (silica, 1 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-c80ddf94ec564abdb31e546099066085
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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