tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate → HCID 86689773, compound

HRID 1396426Notes

Reaction equation

HRID 1396426 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16](Cl)[N:15]=[N:14][C:13]=2[C:19]([NH2:21])=[O:20])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[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:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16]([NH:22][C@@H:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[N:15]=[N:14][C:13]=2[C:19](=[O:20])[NH2:21])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate3×HCID 86689752HCID 86689752, compound

Product 1

HCID 86689773HCID 86689773, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A resealable pressure tube was charged with 4-(6-tert-butylpyridin-2-ylamino)-6-chloropyridazine-3-carboxamide (100 mg, 327 μmol) dissolved in NMP (2.00 mL) To this solution was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (70.7 mg, 327 μmol) and the reaction mixture was heated in an oil bath with stirring at 130° C. for 24 h. Added additional tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (70.7 mg, 327 μmol) and reaction continued for 24 h. Added more tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (70.7 mg, 327 μmol) and reaction continued for 72 h. The NMP was evaporated under high vacuum. The residue was purified by flash chromatography (silica gel 50 μm, 40 g, Analogix) eluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2 to yield tert-butyl (3R,4R)-4-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (73 mg, 46.0% yield) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 11.45 (br. s., 1H), 8.33 (s, 1H), 8.14 (s, 1H), 8.06 (d, J=3.4 Hz, 1H), 7.52 (t, J=7.9 Hz, 1H), 6.91 (d, J=7.9 Hz, 1H), 6.66 (d, J=7.9 Hz, 1H), 5.65 (br. s., 1H), 5.37 (d, J=8.3 Hz, 1H), 3.38-4.31 (m, 6H), 1.63-2.23 (m, 2H), 1.46 (s, 9H), 1.39 (s, 9H); LC-MS 486.3 [M+H]+.

Workup

  1. temperaturethe reaction mixture was heated in an oil bath
  2. additionAdded additional
  3. waitcontinued for 24 h
  4. additionAdded more
  5. waitcontinued for 72 h
  6. customThe NMP was evaporated under high vacuum
  7. customThe residue was purified by flash chromatography (silica gel 50 μm, 40 g, Analogix)
  8. washeluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2

Sources & evidence

ORD record
ord-df823e5e34fa408e87c32bcd93a6ccd6
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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