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

HRID 1529443노트

반응식

HRID 1529443 반응식
[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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 22597222Tetrahydrofuran 2-propanol용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-d8287f95dabb4aba8cfcfdce40cd9ace
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

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