Ammonium Chloride → 5-Fluoro-6-(4-{1-[8-(hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinonitrile

HRID 1424108ノート

反応式

HRID 1424108 の反応式
[Si]([O:8][CH2:9][C:10]1([CH3:38])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26]([C:29]5[C:36]([F:37])=[CH:35][C:32]([C:33]#[N:34])=[CH:31][N:30]=5)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>O1CCCC1>[F:37][C:36]1[C:29]([C:26]2[CH:25]=[CH:24][C:23]([C:20]3([C:17]4[N:13]5[CH2:14][CH2:15][S:16][C:10]([CH2:9][OH:8])([CH3:38])[CH2:11][C:12]5=[N:19][N:18]=4)[CH2:21][CH2:22]3)=[CH:28][CH:27]=2)=[N:30][CH:31]=[C:32]([CH:35]=1)[C:33]#[N:34]

参加物

5

反応物 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 86712955HCID 86712955、化合物

生成物 1

HCID 867129565-Fluoro-6-(4-{1-[8-(hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinonitrile収率 90%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of the compound (451 mg, 0.82 mmol) obtained in Example 71-1) and tetrabutylammonium fluoride (1 M tetrahydrofuran solution, 0.98 mL) in tetrahydrofuran (4 mL) was stirred at room temperature for 18 h. Saturated aqueous ammonium chloride was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (321 mg, 90%) as a colorless solid.

後処理

  1. extractionthe mixture was extracted with dichloromethane
  2. washthe organic layer was washed with saturated sodium chloride solution
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient)

出典と根拠

ORDレコード
ord-e59ca6988cad4267840de5b1cd029eaa
出典データセット
uspto-grants-2015_01
特許番号
US08927536B2

反応ノート

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