Cesium fluoride → 2-(4-Chloro-2-fluoro-3-methoxyphenyl)-6-methoxy-7-methyl-7H-purine

HRID 1969363Notes

Reaction equation

HRID 1969363 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]([CH3:11])[CH:7]=[N:8]2)=[C:4]([O:12][CH3:13])[N:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B2OC(C)(C)C(C)(C)O2)=[C:17]([F:30])[C:16]=1[O:31][CH3:32].[F-].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:2]2[N:10]=[C:9]3[C:5]([N:6]([CH3:11])[CH:7]=[N:8]3)=[C:4]([O:12][CH3:13])[N:3]=2)=[C:17]([F:30])[C:16]=1[O:31][CH3:32]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 134016302-Chloro-6-methoxy-7-methyl-7H-purineHCID 670174932-(4-Chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 591269312-(4-Chloro-2-fluoro-3-methoxyphenyl)-6-methoxy-7-methyl-7H-purineYield 67%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

2-Chloro-6-methoxy-7-methyl-7H-purine (1.2 g, 6.0 mmol, see Monatshefte fuer Chemie (1985), 116(3), 341-51 for preparation), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2.1 g, 8.6 mmol), Pd(PPh3)2Cl2 (300 mg, 0.42 mmol) and cesium fluoride (1.6 g, 11 mmol) were combined in 10 mL dry, deaerated acetonitrile and heated to reflux. After 2 h, the mixture was cooled and mixed with ethyl acetate and water. The organic phase was washed with water, brine, dried and evaporated under vacuum. The residue was purified by flash chromatography on silica gel with 20% ethyl acetate/hexane to give the title compound (1.3 g, 67% yield: mp 191-192° C.: 1H NMR (CDCl3) δ 8.0 (s, 1H), 7.90 (dd, 1H), 7.22 (dd, 1H), 4.22 (s, 3H), 4.08 (s, 3H), 4.02 (s, 3H).

Workup

  1. customdry
  2. temperatureheated to reflux
  3. temperaturethe mixture was cooled
  4. additionmixed with ethyl acetate and water
  5. washThe organic phase was washed with water, brine
  6. customdried
  7. customevaporated under vacuum
  8. customThe residue was purified by flash chromatography on silica gel with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-35959411056342f2ae7322e22fe19a85
Source dataset
uspto-grants-2013_04
Patent number
US08426591B2

Reaction notes

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