Sodium Carbonate → 5-(2-(4-Fluorophenyl)-5-(pyridin-4-yl)thiazol-4-yl)-3-methoxypyridin-2-amine

HRID 1091620Notes

Reaction equation

HRID 1091620 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:14]1[CH:15]=[C:16]([O:21][CH3:22])[C:17]([NH2:20])=[N:18][CH:19]=1.[N:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[S:6][C:2]([C:26]3[CH:27]=[CH:28][N:23]=[CH:24][CH:25]=3)=[C:3]([C:14]3[CH:15]=[C:16]([O:21][CH3:22])[C:17]([NH2:20])=[N:18][CH:19]=3)[N:4]=2)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 665911925-(5-Bromo-2-(4-fluorophenyl)thiazol-4-yl)-3-methoxypyridin-2-amine

Product 1

HCID 591375455-(2-(4-Fluorophenyl)-5-(pyridin-4-yl)thiazol-4-yl)-3-methoxypyridin-2-amineYield 55.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 5-(5-bromo-2-(4-fluorophenyl)thiazol-4-yl)-3-methoxypyridin-2-amine (40 mg, 0.11 mmol), 4-pyridineboronic acid (39 mg, 0.32 mmol), and, and aqueous 2.0 M Na2CO3 solution (0.6 mL) in DME (1.8 mL) was sparged with Ar for 3 min. Tetrakis(triphenylphosphine)palladium(0) (20 mg, 0.02 mmol) was added and the reaction mixture was sparged with Ar for 1 min. The reaction was sealed and irradiated at 115° C. for 15 min in a microwave reactor. The reaction mixture was partitioned with EtOAc (25 mL) and saturated aqueous NaHCO3 solution (25 mL). The separated organic layer was washed with saturated aqueous NaHCO3 solution (25 mL), brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC, which after lypholization, provided 23 mg of the titled compound as the TFA salt: LCMS (m/z): 378.9 (MH+), tR=0.57 min.

Workup

  1. customwas sparged with Ar for 3 min
  2. customthe reaction mixture was sparged with Ar for 1 min
  3. customThe reaction was sealed
  4. customirradiated at 115° C. for 15 min in a microwave reactor
  5. customThe reaction mixture was partitioned with EtOAc (25 mL) and saturated aqueous NaHCO3 solution (25 mL)
  6. washThe separated organic layer was washed with saturated aqueous NaHCO3 solution (25 mL), brine (25 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by reverse phase HPLC, which after lypholization

Sources & evidence

ORD record
ord-02e3e27bfd314caf858b446cbf46b182
Source dataset
uspto-grants-2012_03
Patent number
US08129394B2

Reaction notes

Loading…