Thionyl Chloride → methyl 4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-nitrobenzoate

HRID 571915

Reaction equation

HRID 571915 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[C:7]([N+:14]([O-:16])=[O:15])[CH:6]=1)=[O:4].S(Cl)(Cl)=O.[F:21][C:22]1[CH:23]=[C:24]([CH:36]=[C:37]([F:39])[CH:38]=1)[CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][N:30]=[C:29]2[NH2:35]>C1COCC1.N1C=CC=CC=1>[F:21][C:22]1[CH:23]=[C:24]([CH:36]=[C:37]([F:39])[CH:38]=1)[CH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][N:30]=[C:29]2[NH:35][C:9]([C:8]1[CH:12]=[CH:13][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][C:7]=1[N+:14]([O-:16])=[O:15])=[O:11]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 219064744-(Methoxycarbonyl)-2-nitrobenzoic acidHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amine

Product 1

HCID 68671770methyl 4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-nitrobenzoateYield 65.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(methoxycarbonyl)-2-nitrobenzoic acid (4.8 gr, 21.3 mmol) and thionyl chloride (15.5 mL) were stirred in THF dry (130 mL) at 70° C. for 2 hours. Volatiles were evaporated and the residue dissolved in dry pyridine (100 mL) at 0° C. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (4.6 mg, 17.76 mmol) in dry pyridine (10 mL) was added to the cooled reaction mixture. Temperature was allowed to reach room temperature overnight. Reaction was quenched with NaHCO3 sat. sol and extracted with ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/EtOH/7N NH3 in MeOH=95/5/0.5) affording 5.4 gr (65% yield) of the title compound.

Workup

  1. customdry (130 mL) at 70° C. for 2 hours
  2. customVolatiles were evaporated
  3. dissolutionthe residue dissolved in dry pyridine (100 mL) at 0° C
  4. customReaction
  5. customwas quenched with NaHCO3 sat. sol
  6. extractionextracted with ethyl acetate
  7. dry with materialCollected organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customResidue was purified by column chromatography over silica gel (DCM/EtOH/7N NH3 in MeOH=95/5/0.5)

Sources & evidence

ORD record
ord-6d6b95342a064e458d2c300c49e4dc4a
Source dataset
uspto-grants-2015_05
Patent number
US09029356B2

Linked notes

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