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

HRID 1529443ノート

反応式

HRID 1529443 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 22597222Tetrahydrofuran 2-propanol溶媒

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-d8287f95dabb4aba8cfcfdce40cd9ace
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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