Sodium Iodide → 6-chloro-3-(2,2-difluoro-1-methylcyclopropyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine

HRID 571409노트

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HRID 571409 반응식
[Na+].[I-].[Cl:3][C:4]1[N:9]=[CH:8][C:7]2[C:10]([C:32]([CH3:34])=[CH2:33])=[N:11][N:12]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:5]=1.[F:35][C:36]([Si](C)(C)C)([F:38])F>C1COCC1>[Cl:3][C:4]1[N:9]=[CH:8][C:7]2[C:10]([C:32]3([CH3:34])[CH2:33][C:36]3([F:38])[F:35])=[N:11][N:12]([C:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:6]=2[CH:5]=1

참가 물질

5

반응물 3

HCID 5238Sodium Iodide2회HCID 552549(Trifluoromethyl)trimethylsilane2회HCID 895259366-chloro-3-(prop-1-en-2-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridine

생성물 1

HCID 1176008406-chloro-3-(2,2-difluoro-1-methylcyclopropyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine수율 107%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
65 °C

실험 절차

Reference: Angew. Chemie Int. Ed., 2011, 50(31), 7153. To a 2 dram pressure vial charged with a magnetic stir bar was added anhydrous NaI (3.4 mg, 0.023 mmol), THF (1 ml), and 6-chloro-3-(prop-1-en-2-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (50 mg, 0.115 mmol) under nitrogen. To this was added (trifluoromethyl)trimethylsilane (0.042 ml, 0.287 mmol). The reaction vessel was sealed and heated to 65° C. in an oil bath for a period of 2.5 hours. LCMS and TLC indicated product and remaining starting material. Additional sodium iodide (3.4 mg, 0.023 mmol) and (trifluoromethyl)-trimethylsilane (0.042 ml, 0.287 mmol) were added and the reaction was heated overnight at 65° C. The reaction mixture was concentrated and taken up in ether (15 ml). The organic layer was washed with water (15 ml), saturated sodium thiosulfate solution (15 ml), saturated sodium bicarbonate solution (15 ml), and water (15 ml), in that order. The ethereal layer dried over anhydrous magnesium sulfate, concentrated, and purified (12 g silica gel, eluting with 0-10% tOAc/hexanes) to give 6-chloro-3-(2,2-difluoro-1-methylcyclopropyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (60 mg, 0.123 mmol) as a beige foam. MS ESI calc'd. for C29H22ClF2N3[M+1]+ 486, found 486.

후처리

  1. additionTo a 2 dram pressure vial charged with a magnetic stir bar
  2. customThe reaction vessel was sealed
  3. temperaturethe reaction was heated overnight at 65° C
  4. concentrationThe reaction mixture was concentrated
  5. washThe organic layer was washed with water (15 ml), saturated sodium thiosulfate solution (15 ml), saturated sodium bicarbonate solution (15 ml), and water (15 ml), in that order
  6. dry with materialThe ethereal layer dried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. custompurified
  9. wash(12 g silica gel, eluting with 0-10% tOAc/hexanes)

출처 및 근거

ORD 기록
ord-38acbb2ae10d40499cd011a554ecc333
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09023865B2

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