3-Aminopyridine → 2-[6-(3-Methoxyphenyl)-4-(3-pyridylamino)pyrimidin-2-yl]-1-morpholin-4-ylethan-1-one

HRID 499038Notes

Reaction equation

HRID 499038 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].FC(S(O[C:15]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=2)[N:18]=[C:17]([CH2:29][C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[O:31])[N:16]=1)(=O)=O)(F)F.[NH2:38][C:39]1[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=1>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:28][O:27][C:23]1[CH:22]=[C:21]([C:19]2[N:18]=[C:17]([CH2:29][C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[O:31])[N:16]=[C:15]([NH:38][C:39]3[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=3)[CH:20]=2)[CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 597897656-(3-Methoxyphenyl)-2-(2-morpholin-4-yl-2-oxoethyl)pyrimidin-4-yl (trifluoromethyl)sulfonate

Product 1

HCID 597896702-[6-(3-Methoxyphenyl)-4-(3-pyridylamino)pyrimidin-2-yl]-1-morpholin-4-ylethan-1-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A round bottom flask, oven dried and kept under N2 atmosphere is charged with Cs2CO3 (1.4 eq), Pd(OAc)2 (5 mol %), and S-(−)-BINAP (7.5 mol %). The flask is purged with N2 for about 5-10 min and a solution of compound 9 (1 eq) in dry THF is added via a syringe, followed by 3-aminopyridine (2 eq) in one portion. The flask is equipped with a reflux condenser, purged again with N2 for 5 min and the reaction mixture is refluxed overnight. The reaction mixture is cooled down to room temperature and the solvent is evaporated under reduced pressure. The residue is washed with water (×2) and triturated with methanol to afford the desired 2-[6-(3-methoxyphenyl)-4-(3-pyridylamino)pyrimidin-2-yl]-1-morpholin-4-ylethan-1-one 10.

Workup

  1. customA round bottom flask, oven dried
  2. customThe flask is purged with N2 for about 5-10 min
  3. customThe flask is equipped with a reflux condenser
  4. custompurged again with N2 for 5 min
  5. temperaturethe reaction mixture is refluxed overnight
  6. customthe solvent is evaporated under reduced pressure
  7. washThe residue is washed with water (×2)
  8. customtriturated with methanol

Sources & evidence

ORD record
ord-fb4dfe9b60824191ae2434c4cc391ccc
Source dataset
uspto-grants-2010_08
Patent number
US07767669B2

Reaction notes

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