Hydrochloric Acid → 1H-Indazole

HRID 1625012Notes

Reaction equation

HRID 1625012 reaction equation
[Br-].N[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.C(B(O)O)=C.OC(C(O)(C)C)(C)C.[Li+].[OH-].[CH:24](OC=C)=C.Cl.[CH3:30][N:31](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].C(Cl)Cl>[NH:4]1[C:5]2[C:6](=[CH:7][CH:8]=[CH:3][CH:24]=2)[CH:30]=[N:31]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 8024Vinyl etherHCID 53442856HCID 53442856, compoundHCID 86661507HCID 86661507, compound

Product 1

HCID 92211H-IndazoleYield 78%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of bromide (5b) and pinacol vinylboronate (6, 1.2 equiv) in DMF was added LiOH (3 equiv) followed by PdCl2(dppf).CH2Cl2 (3 mol %). The reaction mixture was heated to 70° C. and stirred for 18 h. HPLC analysis indicated complete conversion to the vinylether intermediate. After cooling the reaction mixture to 50° C., HCl (25%) was added and the mixture was stirred at this temperature for 1 h. The reaction was complete at this point. After workup, compound 8 was isolated as a crystalline solid in 78% yield. MS (Turbo Spray): 231 (35%), 229 (M+H+, 100%).

Workup

  1. temperatureAfter cooling the reaction mixture to 50° C.
  2. stirringthe mixture was stirred at this temperature for 1 h

Sources & evidence

ORD record
ord-e493a866801b44fb9822831b44550bdf
Source dataset
uspto-grants-2014_07
Patent number
US08779150B2

Reaction notes

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