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1,8-Diazabicyclo(5.4.0)undec-7-ene → N-(7-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N'-quinolin-8-ylurea

HRID 1158790
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HRID 1158790 반응식
ClC(Cl)(Cl)[C:3]([NH:5][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[CH:13][CH:12]=[CH:11]2)=[O:4].[C:18]([C:22]1[CH:31]=[C:30]2[C:25]([CH:26]([NH2:32])[CH2:27][CH2:28][O:29]2)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19].N12CCCN=C1CCCCC2>C(#N)C>[C:18]([C:22]1[CH:31]=[C:30]2[C:25]([CH:26]([NH:32][C:3]([NH:5][C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:15]=3[N:14]=[CH:13][CH:12]=[CH:11]4)=[O:4])[CH2:27][CH2:28][O:29]2)=[CH:24][CH:23]=1)([CH3:21])([CH3:19])[CH3:20]
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참가 물질

5

반응물 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27974822,2,2-Trichloro-N-(quinolin-8-YL)acetamideHCID 672368437-tert-Butyl-chroman-4-ylamine

생성물 1

HCID 53251493N-(7-tert-butyl-3,4-dihydro-2H-chromen-4-yl)-N'-quinolin-8-ylurea수율 14.4%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A mixture of the product of Example 3A (145mg, 0.5 mmol), the product of Example 1C (103mg, 0.5 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 190 mg, 1.25 mmol) in acetonitrile (15 mL) was heated at reflux for 3.5 hours, cooled, and the acetonitrile removed under reduced pressure. The residue was taken up in ethyl acetate and washed with water. The isolated organic layer was dried with magnesium sulfate, filtered and the solvent removed under reduced pressure. The resulting residue was purified by reverse-phase HPLC (acetonitrile/water) to give 27 mg of the title compound (14% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 9.37 (s, 1H), 8.83 (dd, J=4.1 and 1.7 Hz, 1H), 8.54 (dd, J=7.3 and 1.9 Hz, 1H), 8.34 (dd, J=8.5 and 1.7 Hz, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.55-7.60 (m, 1H), 7.46-7.53 (m, 2H), 7.22 (d, J=8.1 Hz, 1H), 6.94 (dd, J=8.1 and 2.0 Hz, 1H), 6.77 (d, J=2.0 Hz, 1H), 4.87-4.93 (m, 1H), 4.22-4.29 (m, 1H), 4.12-4.20 (m, 1H), 2.07-2.16 (m, 1H), 1.91-2.00 (m, 1H), 1.24 (s, 9H). MS (ESI) m/e 376 (M+H)+. Calcd. For C23H25N3O2.0.35CF3CO2H: C, 68.53; H, 6.15; N, 10.12. Found C, 68.33; H, 6.00; N, 10.00.

후처리

  1. temperatureat reflux for 3.5 hours
  2. temperaturecooled
  3. customthe acetonitrile removed under reduced pressure
  4. washwashed with water
  5. dry with materialThe isolated organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe resulting residue was purified by reverse-phase HPLC (acetonitrile/water)

출처 및 근거

ORD 기록
ord-1db07bf8aaa340f09cfc43cc6839c9e8
출처 데이터셋
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07812019B2

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