Water → (+/-)-cis-3-[(6-Phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexanol

HRID 2189036Notes

Reaction equation

HRID 2189036 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.CCN(C(C)C)C(C)C.[NH2:26][C@H:27]1[CH2:32][CH2:31][CH2:30][C@H:29]([OH:33])[CH2:28]1.O>CN(C=O)C>[C:11]1([C:9]2[O:8][C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH:26][C@@H:27]4[CH2:32][CH2:31][CH2:30][C@H:29]([OH:33])[CH2:28]4)[C:3]=3[CH:10]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 117882853-Aminocyclohexanol, (1S,3S)-HCID 579464884-Chloro-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 86653748(+/-)-cis-3-[(6-Phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexanol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Heat a mixture of 4.0 g (17.34 mmol) of 4-chloro-6-phenylfuro[2,3-d]pyrimidine, 4.5 ml (26 mmol) of DIEA and 2.8 g of (+/−)-cis/trans-3-aminocyclohexanol (approx. 85% strength, approx. 20.8 mmol; approx. 3:1 cis/trans mixture; prepared according to J. Chem. Soc. Perkin Trans. I, 1994, 537) in 15 ml of DMF is heated to 120° C. overnight. After cooling, add the reaction mixture to water and extract three times with ethyl acetate. Wash the combined organic phases with saturated sodium chloride solution, dry over magnesium sulphate and concentrate under reduced pressure. Repeated stirring of the crude product with a mixture of methyl tert-butyl ether and dichloromethane enriches the product in the mother liquor. After concentrating the mother liquor, filter off the product with suction after crystallization from dichloromethane/methanol (10:1) and dry it under reduced pressure. 1.11 g (20.7% of theory) of the target product are obtained.

Workup

  1. temperatureHeat
  2. temperatureAfter cooling
  3. extractionextract three times with ethyl acetate
  4. washWash the combined organic phases with saturated sodium chloride solution
  5. dry with materialdry over magnesium sulphate
  6. concentrationconcentrate under reduced pressure
  7. concentrationAfter concentrating the mother liquor
  8. filtrationfilter off the product with suction
  9. customafter crystallization from dichloromethane/methanol (10:1)
  10. customdry it under reduced pressure
  11. custom1.11 g (20.7% of theory) of the target product are obtained

Sources & evidence

ORD record
ord-f9cffe85dc554eb5b173dc332165bd8d
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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