Cesium carbonate → (3R,4R)-tert-butyl 4-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yloxy)-3-fluoropiperidine-1-carboxylate

HRID 79305

反応式

HRID 79305 の反応式
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[N:26]=2)[N:4]=1)[CH3:2].[F:32][C@H:33]1[C@@H:38](OS(C)(=O)=O)[CH2:37][CH2:36][N:35]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:34]1.CS(OC1CCN(C(OC(C)(C)C)=O)CC1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[N:26]=[C:27]([O:31][C@@H:38]3[CH2:37][CH2:36][N:35]([C:44]([O:46][C:47]([CH3:49])([CH3:48])[CH3:50])=[O:45])[CH2:34][C@H:33]3[F:32])[CH:28]=[CH:29][CH:30]=2)[N:4]=1)[CH3:2]

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineHCID 52324470Tert-butyl cis-3-fluoro-4-(methylsulfonyloxy)piperidine-1-carboxylateHCID 178437935HCID 178437935、化合物

生成物 1

HCID 67261845(3R,4R)-tert-butyl 4-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yloxy)-3-fluoropiperidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
90 °C

実験手順

To N-(3-ethyl-1-((6-hydroxypyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (25 mg, 0.061 mmol; prepared according to Example 17, Step A) in DMA (2 mL) was added a mixture (approximately 9:1) of (3R,4S)-tert-butyl 3-fluoro-4-(methylsulfonyloxy)piperidine-1-carboxylate (prepared as described in WO 2008/124323) and tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (27 mg). Cs2CO3 (39 mg, 0.12 mmol) was added, the reaction vial was sealed, and the mixture was heated to 90° C. and stirred for 6 hours. DMA was removed under reduce pressure. The residue was diluted with EtOAc (20 mL), washed with saturated NaHCO3 aqueous solution and brine, and concentrated. Silica gel chromatography (DCM/MeOH 10:0.5) gave the desired product (12 mg). (The non-fluorinated product, which was also isolated, was utilized in Example 19, Step A).

後処理

  1. customthe reaction vial was sealed
  2. customDMA was removed
  3. additionThe residue was diluted with EtOAc (20 mL)
  4. washwashed with saturated NaHCO3 aqueous solution and brine
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-b5df516809ac4fe3baef5e8ecb3e0628
出典データセット
uspto-grants-2014_09
特許番号
US08841455B2

関連ノート

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