Formaldehyde → Ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoate

HRID 2067884Notes

Reaction equation

HRID 2067884 reaction equation
[F:1][CH:2]([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:19][CH:18]=3)=[N:14][CH:15]=2)=[CH:6][CH:5]=1.C=O.[C:32]([O-])([O-])=[O:33].[Na+].[Na+]>CS(C)=O.CCOC(C)=O>[F:29][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[N:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH2:32][OH:33])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:19][CH:18]=3)=[N:12][CH:11]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 10340Sodium CarbonateHCID 68727105Ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)acetate

Product 1

HCID 68729053Ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)acetate 31 (1 mmol) and paraformaldehyde (5 mmol.) are dissolved in dry DMSO (0.2-0.5M) and heated at 70° C. in the presence of Na2CO3 (5 mmol.) for 2-6 h until greater than 50% conversion is achieved by LC/MS monitoring. The mixture is diluted with EtOAc and washed with water. After concentration, the residue is purified by silica gel chromatography to yield ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoate 32. MS (m/z) (M+1)+: 432.1.

Workup

  1. washwashed with water
  2. concentrationAfter concentration
  3. customthe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-80604fa1c017485a9d936b69cc406f4c
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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