Tetrahydrofuran → 6-[1-(2-m-Tolyl-ethylamino)-indan-5-yloxy]-nicotinamide

HRID 422236

반응식

HRID 422236 반응식
O=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=3)=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[CH3:21][C:22]1[CH:23]=[C:24]([CH2:28][CH2:29][NH2:30])[CH:25]=[CH:26][CH:27]=1.C1COCC1.[BH3-]C#N.[Na+]>CO.Cl[Ti](Cl)(Cl)Cl>[C:22]1([CH3:21])[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH2:29][NH:30][CH:2]2[C:10]3[C:5](=[CH:6][C:7]([O:11][C:12]4[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=4)=[CH:8][CH:9]=3)[CH2:4][CH2:3]2)[CH:23]=1

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 4100852-(3-Methylphenyl)ethan-1-amineHCID 5003444Sodium cyanoborohydrideHCID 597506396-(1-Oxo-indan-5-yloxy)-nicotinamide2회

생성물 1

HCID 114746936-[1-(2-m-Tolyl-ethylamino)-indan-5-yloxy]-nicotinamide수율 73%

시약·촉매·용매 2

HCID 24193Titanium Tetrachloride촉매HCID 887Methanol용매

실험 절차

Add Ti(iPrO)4 (1.70 g, 6.00 mmol) to a suspension of 6-(1-oxo-indan-5-yloxy)-nicotinamide (Intermediate 4, 805 mg, 3.00 mmol), 2-(3-methylphenyl)ethylamine (446 mg, 3.30 mmol) and THF (20 ml) and stir for six hours under a nitrogen atmosphere at ambient temperature. After cooling in an ice/water bath, treat the reaction mixture with a solution of TiCl4 (1.0M/DCM, 6.00 ml, 6.00 mmol) and stir at 0-5° C. for two hours before adding NaBH3CN (377 mg, 6.00 mmol) dissolved in MeOH (5 ml). Allow the reaction mixture to warm to ambient temperature as the cold bath warms and stir overnight. Quench the reaction with 2N aq. NaOH, making the suspension basic. Stir the suspension for one hour and filter through a filter aid to remove solids, washing them with EtOAc. Separate layers in the filtrate/wash and wash the organic layer with brine before drying (MgSO4) and concentrating. Purify on silica gel (5% (1N NH3/MeOH)/45% EtOAc/DCM) to obtain 849 mg of the title compound as a light yellow solid. Mass spectrum (ion spray): m/z=388 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.15 (d, 1H), 7.30 (d, 1H), 7.19 (t, 1H), 7.05-7.01 (m, 3H), 6.98 (s, 1H), 6.93 (d, 2H), 5.96 (br. s, 2H), 4.26 (t, 1H), 3.02-2.94 (m, 3H), 2.86-2.76 (m, 3H), 2.44 (m, 1H), 2.33 (s, 3H), 1.84 (m, 1H).

후처리

  1. temperatureAfter cooling in an ice/water bath
  2. stirringstir at 0-5° C. for two hours
  3. temperatureto warm to ambient temperature as the cold bath warms
  4. stirringstir overnight
  5. customQuench
  6. customthe reaction with 2N aq. NaOH
  7. stirringStir the suspension for one hour
  8. filtrationfilter through a filter aid
  9. customto remove solids
  10. washwashing them with EtOAc
  11. washSeparate layers in the filtrate/wash
  12. washwash the organic layer with brine
  13. dry with materialbefore drying (MgSO4)
  14. concentrationconcentrating
  15. customPurify on silica gel (5% (1N NH3/MeOH)/45% EtOAc/DCM)

출처 및 근거

ORD 기록
ord-67c268016efd4f248dea5d2a8276b2c3
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101638B2

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