1-Iodonaphthalene → 4-chloro-6-(1-naphthyl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 1678014Notes

Reaction equation

HRID 1678014 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[C:15]2[CH:22]=[CH:21][N:20]([S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)(=[O:25])=[O:24])[C:16]=2[N:17]=[CH:18][N:19]=1.I[C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=[CH:35][CH:34]=1>C1COCC1.CCCCCC.[Cl-].[Zn+2].[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:13][C:14]1[C:15]2[CH:22]=[C:21]([C:41]3[C:42]4[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:38]=[CH:39][CH:40]=3)[N:20]([S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)(=[O:25])=[O:24])[C:16]=2[N:17]=[CH:18][N:19]=1

Participants

9

Reactant 4

HCID 70041-IodonaphthaleneHCID 7912DiisopropylamineHCID 109463064-Chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-D]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 866187344-chloro-6-(1-naphthyl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidineYield 93.2%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of N,N-diisopropylamine (265 μL, 1.89 mmol) in THF (3.00 mL) was added dropwise 1.60 M n-butyllithium in hexane (1.17 mL) at −78° C. under an atmosphere of Argon, and the mixture was stirred for 20 minutes at −78° C. To this mixture was added dropwise a solution of 4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (500 mg, 1.70 mmol) in THF (5.00 mL), and the mixture was stirred for 1 h at −78° C. A solution of zinc chloride (278 mg, 2.04 mmol) in THF (2.00 mL) was added dropwise, and the resulting mixture was taken out the cooling bath and allowed to stir for 1 h. To a suspension of tetrakis(triphenylphosphine)palladium(0) (100 mg, 0.08 mmol) in THF (2.00 mL) was added 1-iodonaphthalene (0.30 mL, 2.06 mmol), and the resulting yellow solution was immediately added to the reaction mixture. The resulting mixture was heated at 80° C. for 1 h. After cooling to 23° C., the reaction mixture was quenched by the addition of water (70.0 mL) and the water layer was acidified with 1.00 M hydrochloric acid. The mixture was extracted with DCM (3×100 mL), and the organic layers were combined. The organic layer was washed with brine, dried over MgSO4, filtered, and evaporated under vacuum. The residue was purified via silica gel column chromatography eluting with 30% ethyl acetate in hexanes to afford the title compound (665 mg, 82%). LC/MS: Rt=11.11 min, ES+ 420.0 (FA long).

Workup

  1. stirringthe mixture was stirred for 1 h at −78° C
  2. stirringto stir for 1 h
  3. additionthe resulting yellow solution was immediately added to the reaction mixture
  4. temperatureThe resulting mixture was heated at 80° C. for 1 h
  5. temperatureAfter cooling to 23° C.
  6. customthe reaction mixture was quenched by the addition of water (70.0 mL)
  7. extractionThe mixture was extracted with DCM (3×100 mL)
  8. washThe organic layer was washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated under vacuum
  12. customThe residue was purified via silica gel column chromatography
  13. washeluting with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-99dfa280b5a049bb8ab38644f6e6a5fe
Source dataset
uspto-grants-2011_08
Patent number
US08008307B2

Reaction notes

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