Potassium Carbonate → HCID 72695484, compound

HRID 1773897Notes

Reaction equation

HRID 1773897 reaction equation
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[CH3:24].[F:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:25][C:26]1[CH:31]=[C:30]([C:2]2[N:11]=[C:10]3[N:4]([CH2:5][CH2:6][C:7]4[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=4[CH:9]3[O:12][CH:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)[C:3]=2[CH3:24])[CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 86703973HCID 86703973, compound

Product 1

HCID 72695484HCID 72695484, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 2-iodo-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 133) (100 mg, 0.23 mmole) in toluene (2 mL) and ethanol (1 mL) in a screw-capped vial are added 3-fluorobenzeneboronic acid (64 mg, 0.46 mmole), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (10 mg) and an 1M aqueous solution of potassium carbonate (0.8 mL). The vial is evacuated and filled with argon. The reaction mixture is stirred at 95° C. for 20 hours. Water is added to the reaction mixture, and the pH is adjusted to 9-10 with 1N aqueous sodium hydroxide. The aqueous phase is extracted three times with ethyl acetate. The pooled organic extracts are dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (95:5:0.1) to (92:8:0.5) to give 2-(3-fluorophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene melting at 132° C.

Workup

  1. customThe vial is evacuated
  2. additionfilled with argon
  3. additionWater is added to the reaction mixture
  4. extractionThe aqueous phase is extracted three times with ethyl acetate
  5. dry with materialThe pooled organic extracts are dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent is removed under reduced pressure
  8. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-6dcd4acc17c54c12a0e5c212727fb019
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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