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

HRID 747989

反応式

HRID 747989 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 24193Titanium Tetrachloride触媒HCID 887Methanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6b4c0924b03f42719e35df9c6a0b7aab
出典データセット
uspto-grants-2008_07
特許番号
US07399774B2

関連ノート

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