Sodium Carbonate → HCID 90403059, compound

HRID 2200715Notes

Reaction equation

HRID 2200715 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][O:23]C3CCCCO3)[C:6](=[O:30])[N:5]([CH3:31])[C:4]=2[N:3]=1.[F:32][C:33]([F:45])([F:44])[O:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.Cl.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>[Cl:18][C:15]1[CH:14]=[CH:13][C:12]([CH2:11][N:10]2[C:9]3[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][OH:23])[C:6](=[O:30])[N:5]([CH3:31])[C:4]=3[N:3]=[C:2]2[C:37]2[CH:38]=[CH:39][CH:40]=[C:35]([O:34][C:33]([F:32])([F:44])[F:45])[CH:36]=2)=[CH:17][CH:16]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 904026828-bromo-7-(4-chlorobenzyl)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione2×

Product 1

HCID 90403059HCID 90403059, compoundYield 49.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 8-bromo-7-(4-chlorobenzyl)-3-methyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-purine-2,6(3H,7H)-dione (100 mg, 0.195 mmol, intermediate 14) in toluene and ethanol (6 mL/2 mL) was added 3-(trifluoromethoxy)phenylboronic acid (60.2 mg, 0.293 mmol) followed by 1 mM aqueous sodium carbonate (1 mL). The mixture was degassed and refilled with a nitrogen atmosphere 3 times. Tetrakis(triphenylphosphine)palladium (12 mg, 0.01 mmol) was added and the reaction was stirred at 100° C. for 16 h. The reaction was cooled and partitioned between ethyl acetate and brine The organic phase was dried and concentrated to give a crude product (110 mg). This crude product was dissolved in 1 mM ethanolic HCl (2 mL) and the mixture was stirred at room temperature for 30 min. The mixture was concentrated and purified by preparative HPLC to give 7-(4-chlorobenzyl)-1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenyl)-1H-purine-2,6(3H,7H)-dione (49 mg, 49.4% yield) as a white solid.

Workup

  1. customThe mixture was degassed
  2. additionrefilled with a nitrogen atmosphere 3 times
  3. temperatureThe reaction was cooled
  4. custompartitioned between ethyl acetate and brine The organic phase
  5. customwas dried
  6. concentrationconcentrated
  7. customto give a crude product (110 mg)
  8. stirringthe mixture was stirred at room temperature for 30 min
  9. concentrationThe mixture was concentrated
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-fcf0e9df959f439fa78b075bd228cbd2
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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