Thionyl Chloride → N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-chlorophenyl)benzoxazole-4-carboxamide

HRID 969824노트

반응식

HRID 969824 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17]([OH:19])=O)[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.Cl.Cl.[N:26]12[CH2:33][CH2:32][CH:29]([CH2:30][CH2:31]1)[CH2:28][CH2:27]2.C([N:37](C(C)C)CC)(C)C>C(Cl)Cl>[N:26]12[CH2:33][CH2:32][CH:29]([CH2:30][CH2:31]1)[CH:28]([NH:37][C:17]([C:13]1[CH:14]=[CH:15][CH:16]=[C:10]3[O:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)=[N:12][C:11]=13)=[O:19])[CH2:27]2

참가 물질

6

반응물 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 18755299Quinuclidine dihydrochlorideHCID 596258542-(4-Chlorophenyl)benzoxazole-4-carboxylic acid

생성물 1

HCID 11523782N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-chlorophenyl)benzoxazole-4-carboxamide수율 17.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A 25 mL round bottomed flask equipped with a reflux condenser was purged with nitrogen and charged with 2-(4-chlorophenyl)benzoxazole-4-carboxylic acid (0.050 g, 0.18 mmol) followed by thionyl chloride (5 mL). The resulting suspension was heated to reflux for 1 hr, after which time a light yellow solution was obtained. The reaction was then cooled and the thionyl chloride removed under reduced pressure affording an off-white solid. This solid was dissolved in methylene chloride (10 mL) and quinuclidine dihydrochloride (0.056 g, 0.27 mmol) added followed by the drop-wise addition of diisopropylethylamine (0.371 g, 2.87 mmol) over 5 min. After stirring at room temperature for 3 hrs the reaction was quenched by the addition of water (10 mL) and the organic layer separated. Subsequent washing of the organic layer with water (10 mL) followed by brine (10 mL), drying over MgSO4, filtration and concentration afforded a tan solid. This solid was purified by preparative HPLC to afford 0.012 g (17% yield) of N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-chlorophenyl)benzoxazole-4-carboxamide as an white solid: mp 194-196° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.13 (m, 1H), 8.23 (dd, J=6.7, 1.9 Hz, 2H), 8.03 (dd, J=8.2, 0.9 Hz, 1H), 7.97 (dd, J=7.7, 0.9 Hz, 1H), 7.78 (dd, J=6.7, 1.9 Hz, 2H), 7.58 (t, J=8.0 Hz, 1H), 4.09 (m, 1H), 3.28 (m, 1H), 2.85 (m, 2H), 2.75 (m, 2H), 2.63 (m, 1H), 2.08 (m, 1H), 1.99 (m, 1H), 1.65 (m, 2H), 1.57 (m, 1H); MS (ESI) m/z 382 [M+H]+.

후처리

  1. customA 25 mL round bottomed flask equipped with a reflux condenser
  2. customwas purged with nitrogen
  3. temperatureThe resulting suspension was heated
  4. temperatureto reflux for 1 hr
  5. customafter which time a light yellow solution was obtained
  6. temperatureThe reaction was then cooled
  7. customthe thionyl chloride removed under reduced pressure
  8. customaffording an off-white solid
  9. customwas quenched by the addition of water (10 mL)
  10. customthe organic layer separated
  11. washSubsequent washing of the organic layer with water (10 mL)
  12. dry with materialdrying over MgSO4, filtration and concentration
  13. customafforded a tan solid
  14. customThis solid was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-47b62dae5a214378a10572e62200f543
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07307094B2

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