1,2-Dichloroethane → 3-iodo-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide

HRID 1529443Notes

Reaction equation

HRID 1529443 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11](O)=[O:12])[CH:9]=2)[N:4]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[N:3]=1.Cl.[CH3:21][NH:22][CH3:23].C(Cl)CCl.Cl>C1COCC1.CC(O)C.CN(C1C=CN=CC=1)C.O>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([N:22]([CH3:23])[CH3:21])=[O:12])[CH:9]=2)[N:4]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[N:3]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 10473Dimethylamine, hydrochlorideHCID 679598343-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid

Product 1

HCID 679599763-iodo-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamideYield 75%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Procedure

To a solution of 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid (2.5 g, 6.72 mmol) and N,N-dimethylamine hydrochloride (0.8 g, 10.08 mmol) in THF:IPA (7:3) (25 mL) was added EDC. HCl (1.5 g, 8.06 mmol) followed by DMAP (341 mg, 2.80 mmol) in one lot at RT. The reaction was stirred at RT for 12 h, diluted with water (50 mL) and extracted with EtOAc (50 mL). The organic layer was separated and dried over Na2SO4, filtered and concentrated to give 3-iodo-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide (2.0 g, 75%) as an off white solid. MS (ESI, pos. ion) m/z: 400.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ 7.82 (d, 1 H, J=8.7 Hz), 7.56 (dd, 1 H, J=8.7, 1.3 Hz), 7.48 (s, 1H), 5.91 (dd, 1 H, J=9.7, 2.0 Hz), 3.89 (d, 1 H, J=11.3 Hz), 3.72-3.78 (m, 1H), 2.99 (s, 6H), 2.37 (dd, 1 H, J=12.4, 9.6 Hz), 1.97-2.04 (m, 2H), 1.72-1.77 (m, 1H), 1.59 (s, 2H).

Workup

  1. extractionextracted with EtOAc (50 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d8287f95dabb4aba8cfcfdce40cd9ace
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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