Cyclopropanecarboxaldehyde → 4-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-(cyclopropyl(hydroxy)-methyl)-2-fluorobenzamide

HRID 1849755노트

반응식

HRID 1849755 반응식
[C:1]12([CH2:11][O:12][C:13]3[C:28](I)=[CH:27][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:26][CH2:25][CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:30])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[Cl-].[Li+].C([Mg]Cl)(C)C.[CH:38]1([CH:41]=[O:42])[CH2:40][CH2:39]1>O1CCCC1>[C:1]12([CH2:11][O:12][C:13]3[C:28]([CH:41]([CH:38]4[CH2:40][CH2:39]4)[OH:42])=[CH:27][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:26][CH2:25][CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:30])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

참가 물질

5

반응물 3

HCID 123114CyclopropanecarboxaldehydeHCID 867036064-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluoro-5-iodobenzamideHCID 178461733HCID 178461733, 화합물2회

생성물 1

HCID 867036374-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-(cyclopropyl(hydroxy)-methyl)-2-fluorobenzamide수율 8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a mixture of 4-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluoro-5-iodobenzamide (0.20 g, 0.36 mmol) in anhydrous tetrahydrofuran (5 mL) was added isopropylmagnesium chloride lithium chloride complex (1.3 M solution in tetrahydrofuran, 0.69 mL, 0.90 mmol) at −40° C. After 1 hour at −40° C., additional isopropylmagnesium chloride lithium chloride complex (1.3 M solution in tetrahydrofuran, 0.28 mL, 0.36 mmol) was added, the reaction mixture warmed to 0° C., and stirred for 1 hour. Cyclopropanecarboxaldehyde (excess) was then added, the reaction mixture was allowed to warm to ambient temperature, and stirred for 16 hours. After quenched with 1 N hydrochloric acid (3 mL), the mixture was diluted with ethyl acetate (50 mL). The combined organic phase was washed with brine (5 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo gave a residue which was purified by reverse-phase preparative HPLC to afford the title compound as a colorless solid (0.015 g, 8%): 1H NMR (300 MHz, DMSO-d6) δ 11.69 (br s, 1H), 7.73 (d, J=8.7 Hz, 1H), 6.91 (d, J=12.7 Hz, 1H), 5.14 (d, J=4.5 Hz, 1H), 4.61 (dd, J=5.7, 4.9 Hz, 1H), 4.02-3.90 (m, 4H), 3.66 (d, J=9.3 Hz, 1H), 3.56 (d, J=9.3 Hz, 1H), 2.19-2.06 (m, 2H), 2.03-1.95 (m, 3H), 1.76-1.57 (m, 12H), 1.18-1.05 (m, 1H), 0.40-0.25 (m, 4H); MS (ES−) m/z 491.2 (M−1).

후처리

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 16 hours
  3. customAfter quenched with 1 N hydrochloric acid (3 mL)
  4. additionthe mixture was diluted with ethyl acetate (50 mL)
  5. washThe combined organic phase was washed with brine (5 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customConcentration of the filtrate in vacuo gave a residue which
  9. customwas purified by reverse-phase preparative HPLC

출처 및 근거

ORD 기록
ord-e41712c9f0864e3b82f48169194d1997
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952169B2

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