1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 58266370, compound

HRID 1506043Notes

Reaction equation

HRID 1506043 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:26])=[N:11][CH:12]=[C:13]([C:15]3[S:23][C:22]4[CH2:21][CH2:20][N:19]([CH2:24][CH3:25])[CH2:18][C:17]=4[CH:16]=3)[CH:14]=2)[CH:3]=1.[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1>[F-].[K+].C(#N)C.C(OCC)(=O)C>[CH2:24]([N:19]1[CH2:20][CH2:21][C:22]2[S:23][C:15]([C:13]3[CH:14]=[C:9]([C:4]4[CH:3]=[C:2]([C:31]5[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=5)[N:7]=[CH:6][C:5]=4[NH2:8])[C:10]([F:26])=[N:11][CH:12]=3)=[CH:16][C:17]=2[CH2:18]1)[CH3:25]

Participants

6

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58266744HCID 58266744, compound

Product 1

HCID 58266370HCID 58266370, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
120 °C

Procedure

A degassed mixture of 6′-chloro-5-(5-ethyl-4,5,6,7-tetrahydro thieno[3,2-c]pyridin-2-yl)-2-fluoro-[3,4′]bipyridinyl-3′-ylamine (1.05 g, 2.70 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (842 mg, 4.10 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (221 mg, 0.27 mmol) in 1N aqueous potassium fluoride solution (9 mL) and acetonitrile (9 mL) was heated under microwave irradiation at 120° C. for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate (100 mL) then washed with water (75 mL). The organic phase was dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 40 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as a white solid (641 mg, 55%). NMR (CDCl3 plus CD3OD, 300 MHz): 8.44 (dd, J=2.5, 1.1 Hz, 1H), 8.13 (d, J=0.6 Hz, 1H), 8.07 (dd, J=8.7, 2.5 Hz, 1H), 7.89 (s, 1H), 7.85 (d, J=0.8 Hz, 1H), 7.32 (s, 1H), 7.12 (s, 1H), 3.94 (s, 3H), 3.61 (s, 2H), 3.00-2.94 (m, 2H), 2.93-2.85 (m, 2H), 2.68 (q, J=7.2 Hz, 2H), 1.21 (t, J=7.2 Hz, 3H).

Workup

  1. customThe cooled reaction mixture
  2. washthen washed with water (75 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto afford a residue that
  7. customwas purified by flash chromatography (silica, 40 g column, ISCO, 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-d9beefc68c3b4038ab74a46e8dd41767
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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