Potassium Phosphate, Tribasic → HCID 22637002, compound

HRID 2416322Notes

Reaction equation

HRID 2416322 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH3:15])C(=O)C(F)(F)F)=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[CH2:39]([O:46][C:47]1[CH:48]=[C:49]([CH:59]=[C:60]([O:63][CH2:64][CH3:65])[C:61]=1I)[CH2:50][C:51]1[C:52]([NH2:58])=[N:53][C:54]([NH2:57])=[N:55][CH:56]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(COC)OC.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.CN(C)C=O>[CH2:39]([O:46][C:47]1[C:61]([C:2]2[CH:3]=[CH:4][C:5]([NH:8][CH3:15])=[CH:6][CH:7]=2)=[C:60]([O:63][CH2:64][CH3:65])[CH:59]=[C:49]([CH2:50][C:51]2[C:52]([NH2:58])=[N:53][C:54]([NH2:57])=[N:55][CH:56]=2)[CH:48]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

9

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 22636804HCID 22636804, compoundHCID 22636806HCID 22636806, compound

Product 1

HCID 22637002HCID 22637002, compoundYield 70.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

N-(4-Bromo-phenyl)-2,2,2-trifluoro-N-methyl-acetamide (2.68 g; 9 mmol), bis(pinacolato)diboron (2.51 g; 9.9 mmol), potassium acetate (2.65 g; 27 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-dichloropalladium(II) (PdCl2(dppf)) (936 mg; 0.81 mmol) are suspended in dimethoxyethane (90 ml; dried over a molecular sieve), and four times the suspension is evacuated with vigorous stirring to remove the oxygen ester and ventilated with argon. The mixture is then stirred at a bath temperature of 80° C. for 24 hours. After cooling to room temperature, dimethylformamide (170 ml), tetrakis-triphenylphosphine-palladium (936 mg; 0.81 mmol), 5-(3-benzyloxy-5-ethoxy-4-iodo-benzyl)-pyrimidine-2,4-diamine (3.42 g; 7.2 mmol) and a 2 M aqueous potassium phosphate solution (36 ml) are added to the reaction mixture. The reaction mixture is stirred for approx. 17 hours under argon at 90° C. (bath temperature), cooled to room temperature and filtered with suction and the filtrate is concentrated. Water (100 ml) is added to the residue obtained and the mixture is extracted with methylene chloride (150 ml). The organic phase is washed successively with water (100 ml and a saturated aqueous sodium chloride solution (100 ml), dried over magnesium sulphate, filtered with suction and concentrated. The residue is chromatographed over silica gel (600 g) with methylene chloride/methanol/NH4OH 19/1/0.05. 2.30 g (47%) 5-(6-benzyloxy-2-ethoxy-4′-methylamino-biphenyl-4-ylmethyl)-pyrimidine-2,4-diamine are obtained as a light-brown powder, which is employed directly in the next stage.

Workup

  1. customdried over a molecular sieve), and four times the suspension
  2. customis evacuated
  3. customto remove the oxygen ester
  4. stirringThe mixture is then stirred at a bath temperature of 80° C. for 24 hours
  5. stirringThe reaction mixture is stirred for approx. 17 hours under argon at 90° C. (bath temperature)
  6. temperaturecooled to room temperature
  7. filtrationfiltered with suction
  8. concentrationthe filtrate is concentrated
  9. additionWater (100 ml) is added to the residue
  10. customobtained
  11. extractionthe mixture is extracted with methylene chloride (150 ml)
  12. washThe organic phase is washed successively with water (100 ml
  13. dry with materiala saturated aqueous sodium chloride solution (100 ml), dried over magnesium sulphate
  14. filtrationfiltered with suction
  15. concentrationconcentrated
  16. customThe residue is chromatographed over silica gel (600 g) with methylene chloride/methanol/NH4OH 19/1/0.05

Sources & evidence

ORD record
ord-97b133d28ba442e089fd1a21969825ac
Source dataset
uspto-grants-2004_11
Patent number
US06821980B1

Reaction notes

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