Hydrochloric Acid → HCID 22479988, compound

HRID 1349902Notes

Reaction equation

HRID 1349902 reaction equation
C[Sn]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]#[N:15])[CH:12]=2)[N:7](C2CCCCO2)[N:6]=1)(C)C.Br[C:23]1[CH:24]=[N:25][C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[CH:28][CH:27]=2.Cl.C(=O)([O-])[O-:35].[K+].[K+]>CN(C)C=O.O.CO.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>[N:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:32]=[C:23]([C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:14]([NH2:15])=[O:35])[CH:12]=3)[NH:7][N:6]=2)[CH:24]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 214133-BromoquinolineHCID 22480164HCID 22480164, compound

Product 1

HCID 22479988HCID 22479988, compoundYield 41%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of the 3-(1,1-dimethyl-1-stannaethyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (0.250 g, 0.64 mmol), 3-bromoquinoline (0.088 mL, 0.64 mmol) and tetrakis(triphenylphosphine)palladium (0.074 g, 0.064 mmol) in N,N-dimethylformamide (5 ml) was heated at 80° C. for 14 h. The mixture was cooled to room temperature, diluted with water and the filtered solid was dried in the vacuum oven. Purification of the solid by column chromatography (silica gel, 30% ethyl acetate/hexanes) gave an intermediate solid which was dissolved in methanol (30 mL). Aqueous 6 N hydrochloric acid (30 mL) was added and the mixture heated at 45° C. for 4 h. The reaction mixture was poured into water, basified with potassium carbonate and the yellow solid collected by suction filtration. A mixture of this product, methanol (20 mL), aqueous 6 N sodium hydroxide (2 mL) and aqueous 30% hydrogen peroxide (3 mL) was heated at 45° C. for 3 h. Water (30 mL) was added and the solid collected. Purification of the residue by preparative HPLC (20–80% acetonitrile/water) gave the title compound (0.075 g, 41% yield): 1H NMR (DMSO-d6) δ 13.73 (s, 1H), 9.61 (d, 1H), 9.01 (s, 1H), 8.81 (s, 1H), 8.22 (m, 2H), 8.11 (d, 1H), 8.02 (d, 1H), 7.83 (t, 1H), 7.71 (t, 2H), 7.43 (br s, 1H); ES-MS (m/z) 289 [M+1]+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customthe filtered solid was dried in the vacuum oven
  3. customPurification of the solid by column chromatography (silica gel, 30% ethyl acetate/hexanes)
  4. customgave an intermediate solid which
  5. temperaturethe mixture heated at 45° C. for 4 h
  6. filtrationthe yellow solid collected by suction filtration
  7. additionA mixture of this product, methanol (20 mL), aqueous 6 N sodium hydroxide (2 mL) and aqueous 30% hydrogen peroxide (3 mL)
  8. temperaturewas heated at 45° C. for 3 h
  9. additionWater (30 mL) was added
  10. customthe solid collected
  11. customPurification of the residue by preparative HPLC (20–80% acetonitrile/water)

Sources & evidence

ORD record
ord-c47ac460496740e9bb60c9b29ad27abf
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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