Methyl chloroformate → 2-(4,4-Difluoro-piperidine-1-carbonyl)-5-(1-isopropyl-piperidin-4-yloxy)-indole-1-carboxylic acid methyl ester

HRID 19845

반응식

HRID 19845 반응식
[F:1][C:2]1([F:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:40][O:41][C:42](Cl)=[O:43]>O1CCCC1.[Cl-].[Na+].O>[CH3:40][O:41][C:42]([N:11]1[C:12]2[C:17](=[CH:16][C:15]([O:19][CH:20]3[CH2:25][CH2:24][N:23]([CH:26]([CH3:27])[CH3:28])[CH2:22][CH2:21]3)=[CH:14][CH:13]=2)[CH:18]=[C:10]1[C:8]([N:5]1[CH2:6][CH2:7][C:2]([F:1])([F:29])[CH2:3][CH2:4]1)=[O:9])=[O:43]

참가 물질

6

반응물 3

HCID 6586Methyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 11603838(4,4-Difluoropiperidin-1-yl)[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]methanone2회

생성물 1

HCID 167394112-(4,4-Difluoro-piperidine-1-carbonyl)-5-(1-isopropyl-piperidin-4-yloxy)-indole-1-carboxylic acid methyl ester수율 15.7%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 57417360Sodium chloride; water용매

실험 절차

A solution of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 100 mg, 1.0 eq.), lithium bis-(trimethylsilyl)amide (1M solution in tetrahydrofuran, 271 ul, 1.1 eq.) and methylchloroformate (26 mg, 1.1 eq.) in tetrahydrofuran (2 mL) was stirred at room temperature for 48 h, then poured into brine, extracted with dichloromethane, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with a 98:2 to 97:3 gradient of dichloromethane/methanol, to yield 18 mg (15%) of the desired product as yellow oil. MS (m/e): 464.2 (MH+, 100%).

후처리

  1. extractionextracted with dichloromethane
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. custompurified on silica gel
  6. washeluting with a 98:2 to 97:3 gradient of dichloromethane/methanol

출처 및 근거

ORD 기록
ord-0b28f7277bb243879e98cc1ec3c71219
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745479B2

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