Hydrochloric Acid → HCID 86653759, compound

HRID 2189059Notes

Reaction equation

HRID 2189059 reaction equation
Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[C:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[OH-].[Na+].[C@H:27]1([OH:33])[CH2:31][CH2:30][C@H:29]([OH:32])[CH2:28]1.Cl>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O.COCCOC>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]2[C:3]3[C:2]([O:32][C@H:29]4[CH2:30][CH2:31][C@H:27]([OH:33])[CH2:28]4)=[N:7][CH:6]=[N:5][C:4]=3[O:8][C:9]=2[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69515251,3-CYCLOPENTANEDIOL, TRANS-HCID 580168154-Chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 86653759HCID 86653759, compound

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Add 1,2-dimethoxyethane to 10 g (29.7 mmol) of 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine in 150 ml of toluene at 70° C. until a homogeneous solution forms. Then add 23.75 g (296.9 mmol) of 50% sodium hydroxide solution and 2.5 ml of water, and, with vigorous stirring, 1.0 g (2.97 mmol) of tetra-n-butylammonium hydrogen sulphate and 4.55 g (44.54 mmol) of (+/−)-cis/trans-1,3-cyclopentanediol, and stir the reaction mixture at 70° C. for 4 h. After cooling, add the mixture to water and neutralize with conc. hydrochloric acid. Extract three times with dichloromethane, wash the combined organic phases with satd. sodium chloride solution, dry over magnesium sulphate and concentrate under reduced pressure. From the residue, chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1→2:1) affords contaminated product. Crystallize this crude product by stirring with methanol. Filter off and dry the resulting crystals (Yield: 690 mg). Concentrate the mother liquor under reduced pressure and purify by preparative RP-HPLC. In this way, a further 1230 mg of the target product are obtained. In total, 1920 mg of the target compound are obtained (16.1% of theory).

Workup

  1. temperatureAfter cooling
  2. extractionExtract three times with dichloromethane
  3. washwash the combined organic phases with satd
  4. dry with materialsodium chloride solution, dry over magnesium sulphate
  5. concentrationconcentrate under reduced pressure
  6. customFrom the residue, chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1→2:1) affords
  7. customCrystallize this crude product
  8. filtrationFilter off
  9. dry with materialdry the resulting crystals (Yield: 690 mg)
  10. concentrationConcentrate the mother liquor under reduced pressure
  11. custompurify by preparative RP-HPLC

Sources & evidence

ORD record
ord-f3bc79f4c2884c91ab6714f014871513
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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