Sodium Carbonate → 5-(3'-Amino-2,6-diethoxy-biphenyl-4-ylmethyl)-pyrimidine-2,4-diamine

HRID 2416295Notes

Reaction equation

HRID 2416295 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:16]=[C:17]([O:20][CH2:21][CH3:22])[C:18]=1I)[CH2:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1)[CH3:2].[NH2:23][C:24]1[CH:25]=[C:26]([B])[CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.C(O)C>[NH2:23][C:24]1[CH:29]=[C:28]([C:18]2[C:4]([O:3][CH2:1][CH3:2])=[CH:5][C:6]([CH2:7][C:8]3[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=3)=[CH:16][C:17]=2[O:20][CH2:21][CH3:22])[CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 201616813-Aminophenyl-boronHCID 226369195-(3,5-Diethoxy-4-iodo-benzyl)-pyrimidine-2,4-diamine

Product 1

HCID 98646205-(3'-Amino-2,6-diethoxy-biphenyl-4-ylmethyl)-pyrimidine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Tetrakis-triphenylphosphine-palladium (555 mg; 0.48 mmol) is suspended in dimethoxyethane (7 ml) while gassing with argon, and 5-(3,5-diethoxy-4-iodo-benzyl)-pyrimidine-2,4-diamine (example 1) (4.14 g; 10 mmol) in dimethoxyethane (60 ml) is added. After stirring for 15 minutes at room temperature, 3-amino-phenylboron acid monnohydrate (2.37 g; 15 mmol) in ethanol (17 ml) is added, the mixture is stirred at room temperature for a further 10 minutes, aqueous 2 M sodium carbonate solution (44 ml) is added and the mixture is then boiled under reflux for 4 hours. The reaction mixture is concentrated and the residue is stirred with water and filtered off with suction. The filter cake is stirred with MeOH (230 ml) and filtered off with suction. The filtrate is concentrated and the residue is chromatographed over silica gel (225 g) with methylene chloride/methanol/ammonia (19/1/0.05, later 90/10/1). The pure fractions are combined and concentrated and the residue is dried under a high vacuum.

Workup

  1. additionis added
  2. stirringthe mixture is stirred at room temperature for a further 10 minutes
  3. temperatureunder reflux for 4 hours
  4. concentrationThe reaction mixture is concentrated
  5. stirringthe residue is stirred with water
  6. filtrationfiltered off with suction
  7. stirringThe filter cake is stirred with MeOH (230 ml)
  8. filtrationfiltered off with suction
  9. concentrationThe filtrate is concentrated
  10. customthe residue is chromatographed over silica gel (225 g) with methylene chloride/methanol/ammonia (19/1/0.05, later 90/10/1)
  11. concentrationconcentrated
  12. customthe residue is dried under a high vacuum

Sources & evidence

ORD record
ord-2d825a8584b74715bba1d95c02d8d6fe
Source dataset
uspto-grants-2004_11
Patent number
US06821980B1

Reaction notes

Loading…