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

HRID 1507108Notes

Reaction equation

HRID 1507108 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(O[I:21](C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.II.OS([O-])=O.[Na+]>C(Cl)Cl>[I:21][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 102317Bis(trifluoroacetoxy)iodobenzeneHCID 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 N-methoxy-N-methyl-1H-indazole-3-carboxamide (CXI) (20 g, 97.4 mmol) in DCM (1 L) was added (Bis(trifluoroacetoxy)iodo)benzene (46 g, 107 mmol) followed by portionwise addition of iodine (14.84 g, 58.5 mmol) at room temperature. After 1 h, saturated aqueous NaHSO3 (600 mL) 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 (CXII) as a white solid (23.2 g, 70 mmol, 72% yield). 1H NMR (DMSO-d6) δ ppm 3.45 (s, 3H), 3.77 (s, 3H), 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-60e1f59276134b9694cb6a242d142355
Source dataset
uspto-grants-2015_12
Patent number
US09221793B2

Reaction notes

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