Sodium Carbonate → HCID 178510349, compound

HRID 40678Notes

Reaction equation

HRID 40678 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[N:9][C:8]([NH:12][C:13]1[N:14]=[CH:15][C:16]([C:19]#[N:20])=[N:17][CH:18]=1)=[CH:7]2.[NH:21]1[CH:25]=[CH:24][C:23](B(O)O)=[N:22]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=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>[NH:21]1[CH:25]=[CH:24][C:23]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[CH:10]=[N:9][C:8]([NH:12][C:13]2[N:14]=[CH:15][C:16]([C:19]#[N:20])=[N:17][CH:18]=2)=[CH:7]3)=[N:22]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 442046545-(8-Bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrileHCID 178514837HCID 178514837, compound

Product 1

HCID 178510349HCID 178510349, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 5-(8-bromoisoquinolin-3-ylamino)pyrazine-2-carbonitrile (65 mg, 0.20 mmol), 1H-pyrazol-3-yl boronic acid (33 mg, 0.30 mmol) and aqueous sodium carbonate (0.5M, 0.60 mL, 0.30 mmol) in DMF (2 mL) was degassed for 15 minutes before the addition of tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.10 mmol). The mixture was further degassed for 5 minutes and then heated to 140° C. for 20 minutes in a microwave reactor. The cooled mixture was partitioned between ethyl acetate and water. The aqueous layer was further extracted with ethyl acetate and the combined organics were washed with water and brine, dried (Na2SO4), and passed sequentially through two PS-Thiol cartridges. The eluent was concentrated to a yellow solid which was dissolved in methanol and purified by SPE on a MP-TsOH cartridge, eluting with 2 M ammonia in methanol. Concentration of the eluent gave the required product as a light yellow solid (18 mg, 0.06 mmol, 29%). 1H NMR (DMSO, 400 MHz) δ 13.25 (br s, 1H), 11.10 (br s, 1H), 10.00 (s, 1H), 8.84 (s, 1H), 8.72 (s, 1H), 8.55 (s, 1H), 7.80-8.00 (m, 2H), 7.70-7.80 (m, 2H), 6.80 (s, 1H). LCMS (2) Rt=2.46 min, m/z (ESI+) 314 (MH+).

Workup

  1. customThe mixture was further degassed for 5 minutes
  2. customThe cooled mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was further extracted with ethyl acetate
  4. washthe combined organics were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationThe eluent was concentrated to a yellow solid which
  7. dissolutionwas dissolved in methanol
  8. custompurified by SPE on a MP-TsOH cartridge
  9. washeluting with 2 M ammonia in methanol

Sources & evidence

ORD record
ord-1e33b8c07add4e5facadc8fc2141cc54
Source dataset
uspto-grants-2013_09
Patent number
US08530468B2

Reaction notes

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