Cesium carbonate → 2-{6-[5-(5-Fluoropyridin-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}pyrimidine

HRID 705040Notes

Reaction equation

HRID 705040 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.[S:9]1[CH:13]=[CH:12][N:11]=[C:10]1[C:14]1[N:19]=[C:18]([C:20]2[N:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[F:8][C:6]1[CH:7]=[C:2]([C:13]2[S:9][C:10]([C:14]3[N:19]=[C:18]([C:20]4[N:21]=[CH:22][CH:23]=[CH:24][N:25]=4)[CH:17]=[CH:16][CH:15]=3)=[N:11][CH:12]=2)[CH:3]=[N:4][CH:5]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 8202063-Bromo-5-fluoropyridineHCID 675166562-[6-(1,3-Thiazol-2-yl)pyridin-2-yl]pyrimidine

Product 1

HCID 675175332-{6-[5-(5-Fluoropyridin-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under argon, 88 mg (0.50 mmol) of 3-bromo-5-fluoropyridine, 120 mg (0.50 mmol) of 2-[6-(1,3-thiazol-2-yl)pyridin-2-yl]pyrimidine (cf. Example K, step 1), 326 mg (1.0 mmol) of cesium carbonate and 8 mg (0.01 mmol) of [(t-Bu)2P(OH)]2PdCl2 (“POPd”) in 10 ml of N,N-dimethylformamide were stirred at 120° C. for 16 hours. For work-up, the solvent was removed under reduced pressure, the residue was partitioned between ethyl acetate and water and the organic phase was dried, concentrated under reduced pressure and purified by column chromatography on silica gel RP-18 (mobile phase: water/acetonitrile/formic acid). This gave 11 mg (7% of theory) of 2-{6-[5-(5-fluoropyridin-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}pyrimidine.

Workup

  1. customFor work-up, the solvent was removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and water
  3. customthe organic phase was dried
  4. concentrationconcentrated under reduced pressure
  5. custompurified by column chromatography on silica gel

Sources & evidence

ORD record
ord-1b8167c4590b46e885db57daa8d00726
Source dataset
uspto-grants-2015_11
Patent number
US09173396B2

Reaction notes

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