Hydrochloric Acid → HCID 136346388, compound

HRID 872046Notes

Reaction equation

HRID 872046 reaction equation
[OH-:1].[K+].Cl[C:4]1[CH:12]=[C:11]([CH2:13][N:14]([CH:22]2[CH2:24][CH2:23]2)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:10]=[C:9]2[C:5]=1[C:6]([CH3:30])=[N:7][N:8]2[CH2:25][CH2:26][CH2:27][O:28][CH3:29].Cl>O.O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[CH:22]1([N:14]([CH2:13][C:11]2[CH:10]=[C:9]3[C:5]([C:6]([CH3:30])=[N:7][N:8]3[CH2:25][CH2:26][CH2:27][O:28][CH3:29])=[C:4]([OH:1])[CH:12]=2)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:24][CH2:23]1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 59494352HCID 59494352, compound

Product 1

HCID 136346388HCID 136346388, compoundYield 95.3%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of potassium hydroxide (41 mg) in water (1 ml) was added to a mixture of tert-butyl {[4-chloro-1-(3-methoxypropyl)-3-methyl-1H-indazol-6-yl]methyl}cyclopropylcarbamate (100 mg), 2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (tBu X-Phos) (8.3 mg), tris(dibenzylideneacetone)dipalladium(0) (9.0 mg) in 1,4-dioxane (1 ml) under argon atmosphere and the mixture was stirred at 100° C. for 90 minutes. A 1N solution of HCl (0.8 ml) and water were added to the reaction mixture under ice-cooling and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate and concentrated in vacuo. The resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane to n-hexane/ethyl acetate=1/2) to give tert-butyl cyclopropyl{[4-hydroxy-1-(3-methoxypropyl)-3-methyl-1H-indazol-6-yl]methyl}carbamate (91 mg) as a pale brown oil.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane to n-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-98433f7093f24755b7b8654cda9d45ef
Source dataset
uspto-grants-2015_03
Patent number
US08975252B2

Reaction notes

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