Sodium Carbonate → HCID 86681764, compound

HRID 715019Notes

Reaction equation

HRID 715019 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[C:15](B4OC(C)(C)C(C)(C)O4)[CH:16]=[C:11]3[C:10]([CH3:26])=[N:9]2)=[CH:5][CH:4]=1.Br[C:30]1[CH:35]=[N:34][CH:33]=[C:32]([Cl:36])[N:31]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(O)C.O.C(OCC)(=O)C.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:36][C:32]1[N:31]=[C:30]([C:15]2[CH:16]=[C:11]3[C:10]([CH3:26])=[N:9][N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:28][CH:27]=4)[C:12]3=[N:13][CH:14]=2)[CH:35]=[N:34][CH:33]=1

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 177505182-Bromo-6-chloropyrazineHCID 57856285HCID 57856285, compound

Product 1

HCID 86681764HCID 86681764, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of (1-(4-methoxybenzyl)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[3,4-b]pyridine) 8 (105 mg, 0.276 mmol) and 2-bromo-6-chloropyrazine 40 (50 mg, 0.268 mmol, 1 equivalent) in DME (3 mL), ethanol (0.5 mL) and water (0.1 mL) was added sodium carbonate (2.0 M, 0.561 mmol, 2 equivalent) and degassed for 10 min followed by charging Pd(PPh3)4 (9.5 mg, 0.0082 mmol, 0.03 equivalent). The resulting reaction mixture was purged with N2 and degassing was submitted for heating at 80° C. overnight under pressure in a sealed tube. After completion of the reaction the reaction was diluted with ethyl acetate and water. The organic layer was separated and aqueous phase was extracted with ethyl acetate. The combined organic layer was washed with brine and dried over sodium sulphate and evaporated. The crude product was flash chromatographed with 100-200 mesh silica gel eluting the pure compound at 40% ethyl acetate in hexane as off white coloured solid of compound 41 in 25 mg. The product 41 was confirmed by LCMS. MS: 365.9, (M+1).

Workup

  1. customdegassed for 10 min
  2. customThe resulting reaction mixture
  3. customwas purged with N2
  4. customdegassing
  5. customAfter completion of the reaction the reaction
  6. customThe organic layer was separated
  7. extractionaqueous phase was extracted with ethyl acetate
  8. washThe combined organic layer was washed with brine
  9. dry with materialdried over sodium sulphate
  10. customevaporated
  11. customchromatographed with 100-200 mesh silica gel eluting the pure compound at 40% ethyl acetate in hexane as off white coloured solid of compound 41 in 25 mg

Sources & evidence

ORD record
ord-16d7f38771034a05b0db67f3a035c893
Source dataset
uspto-grants-2015_11
Patent number
US09187473B2

Reaction notes

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