Iodine → 5-iodo-N-methoxy-N-methyl-1H-indazole-3-carboxamide

HRID 68919

Reaction equation

HRID 68919 reaction equation
[CH3:1][O:2][N:3]([CH3:15])[C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][N:7]=1)=[O:5].FC(F)(F)C(OC1C(OC(=O)C(F)(F)F)=C([I:27])C=CC=1)=O.II.OS([O-])=O.[Na+]>C(Cl)Cl>[I:27][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[NH:8][N:7]=[C:6]2[C:4]([N:3]([O:2][CH3:1])[CH3:15])=[O:5]

Participants

6

Reactant 4

HCID 807IodineHCID 12041285BistrifluoroacetoxyiodobenzeneHCID 16036867N-Methoxy-N-methyl-1H-indazole-3-carboxamideHCID 23665763Sodium Bisulfite

Product 1

HCID 205807385-iodo-N-methoxy-N-methyl-1H-indazole-3-carboxamideYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the N-methoxy-N-methyl-1H-indazole-3-carboxamide (IX) (20 g, 97.4 mmol) in 1 L DCM was added bis(trifluoroacetoxy)iodobenzene (46 g, 107 mmol) followed by portionwise addition of iodine (14.84 g, 58.5 mmol) at r.t. After 1 hour, 600 mL of saturated NaHSO3 was added and a solid began to precipitate which was filtered and rinsed with excess DCM. The filtrate was washed with brine, dried over MgSO4, concentrated and the remaining solid was triturated with a minimal amount of DCM. The combined solids were dried under vacuum over KOH to produce 5-iodo-N-methoxy-N-methyl-1H-indazole-3-carboxamide (X) as a white solid (23.2 g, 70 mmol, 72% yield). 1H NMR (DMSO-d6) δ ppm 3.45 (s, 4H), 3.77 (s, 4H), 7.45-7.54 (m, 1H), 7.66 (dd, J=8.81, 1.51 Hz, 1H), 8.40 (d, J=1.01 Hz, 1H); ESIMS found for C10H10IN3O2 m/z 331 (M+H).

Workup

  1. customto precipitate which
  2. filtrationwas filtered
  3. washrinsed with excess DCM
  4. washThe filtrate was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customthe remaining solid was triturated with a minimal amount of DCM
  8. dry with materialThe combined solids were dried under vacuum over KOH

Sources & evidence

ORD record
ord-8661c5eb07474683b1435d57239cbbd1
Source dataset
uspto-grants-2014_09
Patent number
US08822478B2

Linked notes

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