Sodium Carbonate → 2-(5-Chloro-2-fluoro-phenyl)-4-isoquinolin-4-yl-[1,8]naphthyridine

HRID 1404311Notes

Reaction equation

HRID 1404311 reaction equation
Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[F:19])[CH:3]=1.[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](B(O)O)=[CH:22][N:21]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[Cl:18][C:16]1[CH:15]=[CH:14][C:13]([F:19])=[C:12]([C:4]2[CH:3]=[C:2]([C:23]3[C:24]4[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:20]=[N:21][CH:22]=3)[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 3761204Isoquinoline-4-boronic acidHCID 533447244-Chloro-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine

Product 1

HCID 666317532-(5-Chloro-2-fluoro-phenyl)-4-isoquinolin-4-yl-[1,8]naphthyridineYield 77.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

426 mg 4-chloro naphthyridine from example 1, 682 mg 4-isoquinoline boronic acid pinacole ester, 945 mg sodium carbonate were dissolved with 30 ml dioxan and 3 ml water, flushed with nitrogen, and 172 mg tetrakistriphenylphosphine palladium(0) were added. After 105 min reflux workup as in example 20 yielded a brownish oil, which was crystallized with ether to give 436 mg of product with correct LC-MS: M+H+ 386 and Rt˜2.22 min.

Workup

  1. customflushed with nitrogen, and 172 mg tetrakistriphenylphosphine palladium(0)
  2. additionwere added
  3. temperatureAfter 105 min reflux workup as in example 20
  4. customyielded a brownish oil, which
  5. customwas crystallized with ether

Sources & evidence

ORD record
ord-2431ab0be9644dd088df07261bc136d6
Source dataset
uspto-grants-2014_12
Patent number
US08912216B2

Reaction notes

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