Potassium tert-butoxide → HCID 56971111, compound

HRID 2278445Notes

Reaction equation

HRID 2278445 reaction equation
CN(C)[CH:3]=[C:4]([C:13]1[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[CH:14]=1)[C:5]([C:7]1[CH:11]=[CH:10][O:9][C:8]=1[CH3:12])=O.Cl.[CH3:22][CH:23]1[O:28][CH:27]([CH3:29])[CH2:26][N:25]([C:30](=[NH:32])[NH2:31])[CH2:24]1.CC(C)([O-])C.[K+]>C(O)C>[CH3:29][C@H:27]1[O:28][C@@H:23]([CH3:22])[CH2:24][N:25]([C:30]2[N:31]=[C:5]([C:7]3[CH:11]=[CH:10][O:9][C:8]=3[CH3:12])[C:4]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[CH:14]=3)=[CH:3][N:32]=2)[CH2:26]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 67513546HCID 67513546, compoundHCID 67513884HCID 67513884, compound

Product 1

HCID 56971111HCID 56971111, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3-(dimethylamino)-1-(2-methyl-3-f uranyl)-2-(2-methyl-4-pyridinyl)-2-propen-1-one (1352 mg, 5 mmol) and 2,6-dimethyl-4-morpholinecarboximidamide hydrochloride (1453 mg, 7.50 mmol) (ca. 2.3:1 mixture of cis:trans isomers) in ethanol (10 ml) was stirred at room temperature. Potassium tert-butoxide (1122 mg, 10.00 mmol) was added and the mixture was heated at reflux for 3 hours. After cooling to room temperature the solvent was evaporated and the residue was diluted with water and extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 50% ethyl acetate in isohexane to give cis-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine as an oil (200 mg). The cross-over fractions from the column (˜800 mg) were purified by mass-directed automated HPLC to give additional cis-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine (200 mg) and trans-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine (49 mg). A solution of cis-2,6-dimethyl-4-[4-(2-methyl-3-furanyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine (200 mg, 0.55 mmol) was dissolved in dichloromethane (2 ml) and hydrogen chloride (1M in ether, 0.6 ml) was added. The solvent was evaporated and the residue was evaporated with ether (×2) and then triturated with ether. The solid was collected, washed with ether and dried to give the title compound (178 mg). LC/MS [M+H]+=365. 1H NMR (400 MHz, d6-DMSO): δ 8.61 (1H, d), 8.56 (1H, s), 7.82 (1H, b), 7.58-7.53 (1H, m), 7.52 (1H, d), 6.04 (1H, d), 4.65-4.58 (2H, m), 3.64-3.55 (2H, m), 2.72-2.63 (2H, m), 2.66 (3H, s), 2.36 (3H, s), 1.18 (6H, d).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 3 hours
  3. temperatureAfter cooling to room temperature the solvent
  4. customwas evaporated
  5. additionthe residue was diluted with water
  6. extractionextracted with ethyl acetate
  7. washwashed with water and brine
  8. customdried
  9. customevaporated
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-5fa7af3cc28f4893a87ddabb86b21c61
Source dataset
uspto-grants-2015_09
Patent number
US09133178B2

Reaction notes

Loading…