Pyridine → 4-Butyl-n-{2-[methyl-(1-methyl-piperidin-4-yl)-amino]-benzooxazol-5-yl}-benzamide

HRID 1174937

반응식

HRID 1174937 반응식
C(Cl)(=O)C(Cl)=O.[CH2:7]([C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1)[CH2:8][CH2:9][CH3:10].[CH3:20][N:21]([CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1)[C:22]1[O:23][C:24]2[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][C:25]=2[N:26]=1.N1C=CC=CC=1>CN(C=O)C.C(Cl)Cl>[CH2:7]([C:11]1[CH:12]=[CH:13][C:14]([C:15]([NH:31][C:28]2[CH:29]=[CH:30][C:24]3[O:23][C:22]([N:21]([CH3:20])[CH:32]4[CH2:33][CH2:34][N:35]([CH3:38])[CH2:36][CH2:37]4)=[N:26][C:25]=3[CH:27]=2)=[O:17])=[CH:18][CH:19]=1)[CH2:8][CH2:9][CH3:10]

참가 물질

7

반응물 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 886314-Butylbenzoic acidHCID 59558009N2-Methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine

생성물 1

HCID 115100164-Butyl-n-{2-[methyl-(1-methyl-piperidin-4-yl)-amino]-benzooxazol-5-yl}-benzamide수율 38.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

실험 절차

Add oxalyl chloride (0.16 mL, 1.82 mmol) and 3 drops of DMF to a stirring suspension of 4-butyl-benzoic acid (0.162 g, 0.910 mmol) in CH2Cl2 (2.0 mL). Stir the reaction mixture at room temperature for 2 h. Concentrate the mixture in vacuo, add n-hexane, re-concentrate, and re-dissolve in CH2Cl2. Add the resultant 4-butyl-benzoyl chloride solution to a mixture of rac-N2-methyl-N2-(1-methyl-piperidin-4-yl)-benzooxazole-2,5-diamine (0.158 g, 0.607 mmol) and pyridine (0.05 mL) in CH2Cl2 (10 mL). Shake the reaction mixture overnight at room temperature. Wash the mixture with saturated NaHCO3 (aq) (2×20 mL), dry the organic phase over Na2SO4, filter, and concentrate the mixture in vacuo. Subject the residue to silica gel flash column chromatography (3×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2) to yield the desired product as an oil (0.098 g, 35%). mass spectrum (m/e): 421.0 (M+1). 1H NMR (400 MHz, CDCl3): δ 7.84-7.78 (m, 1H), 7.78 (d, J=8.0 Hz, 2H), 7.48 (d, J=1.9 Hz, 1H), 7.35 (dd, J 8.8, 1.8 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.20 (d, J=8.8 Hz, 1H), 4.21-4.11 (m, 1H), 3.07 (s, 3H), 2.97 (d, J=11.2 Hz, 2H), 2.66 (t, J=8.0 Hz, 2H), 2.32 (s, 3H), 2.17 (t, J=11.6 Hz, 2H), 2.01-1.87 (m, 2H), 1.83-1.75 (m, 2H), 1.65-1.56 (m, 2H), 1.40-1.30 (m, 2H), 0.92 (t, J=7.2 Hz, 3H).

후처리

  1. concentrationConcentrate the mixture in vacuo
  2. additionadd n-hexane
  3. concentrationre-concentrate
  4. dissolutionre-dissolve in CH2Cl2
  5. additionAdd the resultant 4-butyl-benzoyl chloride solution
  6. customthe reaction mixture overnight
  7. customat room temperature
  8. washWash the mixture with saturated NaHCO3 (aq) (2×20 mL)
  9. dry with materialdry the organic phase over Na2SO4
  10. filtrationfilter
  11. concentrationconcentrate the mixture in vacuo
  12. washto silica gel flash column chromatography (3×4 g columns, eluting with 5% 2N NH3 in MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-62bb5c01edc8440eae3cdc3efc763181
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07838543B2

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