Triisopropyl borate → 4-Chloro-7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidine

HRID 611541Notes

Reaction equation

HRID 611541 reaction equation
[Cl:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[O:17]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[B-](F)(F)F)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[K+].O(C1C=CC=CC=1Br)C1C=CC=CC=1.C([Li])CCC.B(OC(C)C)(OC(C)C)OC(C)C.F.[K].C(=O)(O)[O-].[Na+]>O1CCCC1.C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O.C(O)C>[Cl:1][C:2]1[C:3]2[C:10]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[O:17][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[CH:9][N:8]([CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

13

Reactant 7

HCID 21531Triisopropyl borateHCID 374831-Bromo-2-phenoxy-benzeneHCID 516892Sodium BicarbonateHCID 195974344-Chloro-7-cyclopentyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidineHCID 53443437Potassium fluoride, 99%, spray-driedHCID 117064613Potassium trifluoro(2-phenoxyphenyl)boranuideHCID 178418339Butyllithium

Product 1

HCID 195975124-Chloro-7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 5

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 4-chloro-7-cyclopentyl-5-iodopyrrolo[2,3-d]pyrimidine (1.26 g) and potassium (2-phenoxyphenyl)trifluoroborate (1.0 g, prepared by reacting 2-phenoxybromobenzene with butyllithium in tetrahydrofuran at -70° C. followed by triisopropyl borate (IV) followed by potassium hydrogen fluoride by a method analogous to that described in J. Org. Chem. 1995, 60, 3020-3027), in degassed toluene (40 ml), ethanol (10 ml) and water (10 ml) was stirred under nitrogen and bis(triphenylphosphine)palladium (II) chloride (0.25 g) was added followed by sodium bicarbonate (2.0 g). The mixture was stirred and heated at 105° C. for 16 hours and then cooled to ambient temperature. The mixture was separated and the upper layer was evaporated under reduced pressure to give a residue which was purified by flash column chromatography on silica using petroleum ether/ether (2:1) as a mobile phase to give 4-chloro-7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidine which was used directly in the next part of this example.

Workup

  1. customprepared
  2. customat -70° C.
  3. temperaturecooled to ambient temperature
  4. customThe mixture was separated
  5. customthe upper layer was evaporated under reduced pressure
  6. customto give a residue which
  7. customwas purified by flash column chromatography on silica

Sources & evidence

ORD record
ord-b4eebe3eee174287b4ef969442b773b5
Source dataset
uspto-grants-1999_12
Patent number
US06001839

Reaction notes

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