Hydrochloric Acid → HCID 76284978, compound

HRID 1778769Notes

Reaction equation

HRID 1778769 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[C:13]1[CH:14]=[C:15]2[N:21](C3CCCCO3)[N:20]=[C:19](I)[C:16]2=[N:17][CH:18]=1.[CH3:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.C(Cl)(=O)C>O1CCOCC1.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>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[C:13]1[CH:14]=[C:15]2[NH:21][N:20]=[C:19]([C:33]3[CH:32]=[N:31][N:30]([CH3:29])[CH:34]=3)[C:16]2=[N:17][CH:18]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86722865HCID 86722865, compound

Product 1

HCID 76284978HCID 76284978, compoundYield 20.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[4,3-b]pyridine (25 mg, 0.047 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (12 mg, 0.056 mmol), tetrakis(triphenylphosphine)palladium(0) (3 mg, 0.002 mmol), and cesium carbonate (46 mg, 0.14 mmol) in 1,4-dioxane (0.5 mL) and water (0.07 mL) in a reaction vial was degassed, sealed, and stirred at 85° C. for 3 h. After cooling the mixture was concentrated and the residue was dissolved in methanol (0.4 mL, 10 mmol). To the solution was added HCl solution previously prepared from acetyl chloride (0.3 mL) in methanol (0.3 mL). The mixture was stirred at r.t. for 1 h then concentrated, diluted with methanol, and purified by RP-HPLC (pH=2) to afford the desired product (3.9 mg) as a TFA salt. LCMS (M+H)+=404.1.

Workup

  1. customin a reaction
  2. customvial was degassed
  3. customsealed
  4. temperatureAfter cooling the mixture
  5. concentrationwas concentrated
  6. stirringThe mixture was stirred at r.t. for 1 h
  7. concentrationthen concentrated
  8. additiondiluted with methanol
  9. custompurified by RP-HPLC (pH=2)

Sources & evidence

ORD record
ord-352e8a6c4178457794ddb81fc7d4ddf8
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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