Thiophene-3-boronic acid → 3-Methyl-1-(2-methylpropyl)-5-(3-thienyl)-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 2181353Notes

Reaction equation

HRID 2181353 reaction equation
Br[C:2]1[C:10]2[C:9](=[O:11])[N:8]([CH3:12])[C:7](=[O:13])[N:6]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:5]=2[S:4][C:3]=1[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]([F:28])([F:27])[F:26].[S:29]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30]1.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][N:8]1[C:9](=[O:11])[C:10]2[C:2]([C:31]3[CH:32]=[CH:33][S:29][CH:30]=3)=[C:3]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]([F:28])([F:27])[F:26])[S:4][C:5]=2[N:6]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:7]1=[O:13]

Participants

7

Reactant 3

HCID 581760Thiophene-3-boronic acidHCID 114429025-Bromo-1-isobutyl-3-methyl-6-[2-(trifluoromethyl)benzyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneHCID 17749109Barium hydroxide, octahydrate

Product 1

HCID 101627123-Methyl-1-(2-methylpropyl)-5-(3-thienyl)-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, (0.35 g, Example 1c)), thiophene-3-boronic acid (0.053 g), barium hydroxide octahydrate (0.15 g) and tetrakis(triphenylphosphine)palladium (0) (0.0097 g) in ethylene glycol dimethyl ether (6 ml) and water (1 ml) were combined in a sealed vial and stirred with heating at 80° C. for 18 hours. After cooling, the reaction mixture was absorbed onto silica and purified by flash silica chromatography eluting with 25% ethyl acetate in isohexane to give an oil. The oil was triturated with isohexane, filtered and dried under vacuum to give the title compound as a beige solid (0.020 g).

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was absorbed onto silica
  3. custompurified by flash silica chromatography
  4. washeluting with 25% ethyl acetate in isohexane
  5. customto give an oil
  6. customThe oil was triturated with isohexane
  7. filtrationfiltered
  8. customdried under vacuum

Sources & evidence

ORD record
ord-c44730b3897b4e79bc6e9a8684832b1a
Source dataset
uspto-grants-2005_05
Patent number
US06890923B2

Reaction notes

Loading…