Hydrochloric Acid → Hydrochloric Acid

HRID 499037Notes

Reaction equation

HRID 499037 reaction equation
[N:1]1([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)[CH:10]=[C:9]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([O:26]CC4C=CC=CC=4)[CH:21]=3)[N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(#N)C.[ClH:37]>C(O)C>[N:1]1([C:7]2[N:8]=[C:9]([C:20]3[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=3)[CH:10]=[C:11]([NH:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)[N:12]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1.[ClH:37]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 9980614HCID 9980614, compound

Product 2

HCID 313Hydrochloric AcidHCID 104055253-[2-Morpholin-4-yl-6-(pyridin-3-ylamino)pyrimidin-4-yl]phenol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

{2-Morpholin-4-yl-6-[3-(phenylmethoxy)phenyl]pyrimidin-4-yl}-3-pyridylamine (1 eq) is suspended in ethanol in a round bottom flask, purged with N2. 10% Pd/C (20% wt) was added. The flask was evacuated and filled up with H2 (contained in a balloon) for five times, then the reaction mixture was stirred under H2 for 20 h. The catalyst was filtered off through a pad of celite washing thoroughly with EtOH, MeOH, CH2Cl2, and acetonitrile (almost one liter of the mixture of solvents was used to ensure the complete solubilization of the product). The solvent was evaporated under reduced pressure and the residue purified by reverse phase chromatography (Buffer A: 0.1% TFA in H2O, Buffer B: 0.1% TFA in CH3CN; Column: Waters, C18, 47×300 mm; gradient: 1.1%, 10%-60% B in 45 min). The free base thus obtained was lyophilized from a 1:1 mixture of acetonitrile and 1N HCl, obtaining the desired 3-[2-morpholin-4-yl-6-(3-pyridylamino)pyrimidin-4-yl]phenol as the bis HCl salt. The spectral data are the following:

Workup

  1. custompurged with N2
  2. addition10% Pd/C (20% wt) was added
  3. customThe flask was evacuated
  4. additionfilled up with H2 (
  5. filtrationThe catalyst was filtered off through a pad
  6. washof celite washing thoroughly with EtOH, MeOH, CH2Cl2, and acetonitrile (almost one liter of the mixture of solvents
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue purified by reverse phase chromatography (Buffer A: 0.1% TFA in H2O, Buffer B
  9. waitgradient: 1.1%, 10%-60% B in 45 min)
  10. customThe free base thus obtained

Sources & evidence

ORD record
ord-0f21e79876974e48af7e8634ebb20f65
Source dataset
uspto-grants-2010_08
Patent number
US07767669B2

Reaction notes

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