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

HRID 1849755ノート

反応式

HRID 1849755 の反応式
[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

参加物

5

反応物 3

HCID 123114CyclopropanecarboxaldehydeHCID 867036064-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluoro-5-iodobenzamideHCID 178461733HCID 178461733、化合物2 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e41712c9f0864e3b82f48169194d1997
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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