Cesium carbonate → 5-(2,4-Difluorophenoxy)-1-isobutyl-6-(morpholin-2-ylmethoxy)-1H-indazole

HRID 909193

反応式

HRID 909193 の反応式
[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[OH:14])[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2.C([O-])([O-])=O.[Cs+].[Cs+].C(OC([N:37]1[CH2:42][CH2:41][O:40][CH:39]([CH2:43]Br)[CH2:38]1)=O)(C)(C)C>CC(N(C)C)=O.CCOCC.O>[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[O:14][CH2:43][CH:39]1[O:40][CH2:41][CH2:42][NH:37][CH2:38]1)[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 57418765tert-Butyl 2-(bromomethyl)morpholine-4-carboxylateHCID 1361636625-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol

生成物 1

HCID 674102795-(2,4-Difluorophenoxy)-1-isobutyl-6-(morpholin-2-ylmethoxy)-1H-indazole

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol (0.035 g, 0.11 mmol) in DMA (3.5 mL) was added Cs2CO3 (0.11 g, 0.33 mmol). The mixture stirred at room temperature for 1 hour before the addition of 2-bromomethylmorpholine-4-carboxylic acid tert-butyl ester (0.062 g, 0.22 mmol). The resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was diluted with ether and water and the layers were separated. The aqueous layer was extracted with ether (3×) and the combined organic layers were washed with water and brine, and dried over Na2SO4. The crude mixture was concentrated under reduced pressure and purified by reverse phase HPLC to afford the desired product. MS (APCI+) m/z 418 (M+1) detected; 1H NMR (400 mHz, CD3OD) δ 7.90 (s, 1H), 7.38 (s, 1H), 7.21 (s, 1H), 7.11 (m, 1H), 6.84 (m, 2H), 4.22 (m, 2H), 4.18 (d, 2H), 4.05 (m, 2H), 3.31 (m, 3H), 3.03 (m, 2H), 2.31 (m, 1H), 0.92 (d, 6H)

後処理

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with ether (3×)
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationThe crude mixture was concentrated under reduced pressure
  6. custompurified by reverse phase HPLC

出典と根拠

ORDレコード
ord-f6fee2ee43ae4e31945ed45a62aa7267
出典データセット
uspto-grants-2011_09
特許番号
US08017641B2

関連ノート

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