Hydrazine → HCID 178501787, compound

HRID 1673014Notes

Reaction equation

HRID 1673014 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([OH:6])=[N:2]1.NN.BrC1SC([C:15](=[O:17])[CH3:16])=CC=1.[C:18](=O)(OC)[O:19]C.[H-].[Na+].Cl.NN>CO.CCOCC>[CH3:18][O:19][C:15](=[O:17])[CH2:16][O:6][C:3]1[CH:4]=[CH:5][NH:1][N:2]=1

Participants

9

Reactant 6

HCID 9321HydrazineHCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 793352-Acetyl-5-bromothiopheneHCID 115031Hydrazinium chlorideHCID 178516538HCID 178516538, compound2×

Product 1

HCID 178501787HCID 178501787, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

As depicted in Scheme 15, pyrazole-3-ol (15C) was prepared via the condensation of ketoester 15B with a hydrazine and then was alkylated to afford ether analogs. β-ketoester 15B was prepared by treating 1-(5-bromo-thiophen-2-yl)ethanone 15A with dimethyl carbonate in the presence of NaH. The resulting O-ketoester 15B and a hydrazine hydrochloride was heated to reflux in MeOH to give a mixture of 1H-pyrazole-3-ol 15C and the corresponding 3-methoxy-1H-pyrazole, which can be separated by chromatography. 15C reacted with methyl bromoacetate in the presence of K2CO3 in DMF to give [1H-pyrazol-3-yloxy]-acetic acid methyl ester 15D, which was treated with 3-methanesulfonylphenylboronic acid in the presence of Pd (PPh3)4 and aq Na2CO3 in THF to give Suzuki coupling product 15E. Ester 15E was hydrolyzed with aq NaOH in MeOH to afford acid 15F.

Workup

  1. customto give
  2. customthe corresponding 3-methoxy-1H-pyrazole, which can be separated by chromatography
  3. custom15C reacted with methyl bromoacetate in the presence of K2CO3 in DMF

Sources & evidence

ORD record
ord-62d001711f21487fbe7ecbc8f2ae0727
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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