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

HRID 1529443Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529443
[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

Komponenten

8

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 22597222Tetrahydrofuran 2-propanolLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-d8287f95dabb4aba8cfcfdce40cd9ace
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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