2,6-Lutidine → 7-[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazol-3-yl]-2-(4-methoxy-benzyl)-5-methyl-2H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one

HRID 1907146Notes

Reaction equation

HRID 1907146 reaction equation
[NH2:1][C:2]1[C:3]([CH3:23])=[CH:4][C:5]2[C:9]([C:10]=1[C:11]([OH:13])=[O:12])=[N:8][N:7]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)[CH:6]=2.[Cl:24][C:25]1[C:26]([N:31]2[C:35]([C:36](O)=O)=[CH:34][C:33]([O:39][CH3:40])=[N:32]2)=[N:27][CH:28]=[CH:29][CH:30]=1.C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.CS(Cl)(=O)=O>C(#N)C>[Cl:24][C:25]1[C:26]([N:31]2[C:35]([C:36]3[O:12][C:11](=[O:13])[C:10]4[C:9]5=[N:8][N:7]([CH2:14][C:15]6[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=6)[CH:6]=[C:5]5[CH:4]=[C:3]([CH3:23])[C:2]=4[N:1]=3)=[CH:34][C:33]([O:39][CH3:40])=[N:32]2)=[N:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 31297Methanesulfonyl chlorideHCID 65578Oxalyl chlorideHCID 509892861-(3-chloropyridin-2-yl)-3-methoxy-1H-pyrazole-5-carboxylic acidHCID 585004296-amino-2-(4-methoxy-benzyl)-5-methyl-2H-indazole-7-carboxylic acid

Product 1

HCID 585004627-[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazol-3-yl]-2-(4-methoxy-benzyl)-5-methyl-2H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 6-amino-2-(4-methoxy-benzyl)-5-methyl-2H-indazole-7-carboxylic acid (0.288 g, 0.925 mmol) in acetonitrile (4 ml) was stirred at 20° C. for 10 minutes before the acyl chloride prepared from 2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carboxylic acid and oxalyl chloride (0.265 g, 0.971 mmol) was added. After 45 minutes stirring, 2,6-lutidine (0.215 ml) was added, followed 10 minutes later by methanesulfonyl chloride (0.072 ml, 0.925 mmol). After 18 hours of reaction, the mixture was concentrated under vacuum and water (25 ml) was added. The product was extracted with ethyl acetate and purified by flash chromatography on silica gel using a gradient from 50% to 100% ethyl acetate in cyclohexane. The desired product was obtained as light orange crystals.

Workup

  1. additionwas added
  2. customAfter 18 hours of reaction
  3. concentrationthe mixture was concentrated under vacuum and water (25 ml)
  4. additionwas added
  5. extractionThe product was extracted with ethyl acetate
  6. custompurified by flash chromatography on silica gel using a gradient from 50% to 100% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-ea766e1c642f40588e83d01e65061c7f
Source dataset
uspto-grants-2013_12
Patent number
US08598078B2

Reaction notes

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