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 1424108노트

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HRID 1424108 반응식
[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]

참가 물질

5

반응물 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 86712955HCID 86712955, 화합물

생성물 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)nicotinonitrile수율 90%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e59ca6988cad4267840de5b1cd029eaa
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927536B2

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