Ethyl Acetate → 6-(2-(3,3-dimethylbutyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

HRID 130922노트

반응식

HRID 130922 반응식
[CH2:1]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)=[CH:11][C:6]=2[CH2:5][CH2:4][CH2:3][NH:2]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32].C(OCC)(=O)C>CN(C=O)C>[CH3:32][C:31]([CH3:34])([CH3:33])[CH2:30][CH2:29][N:2]1[CH2:3][CH2:4][CH2:5][C:6]2[CH:11]=[C:10]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)[CH:9]=[CH:8][C:7]=2[CH2:1]1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 1371371-Bromo-3,3-dimethylbutaneHCID 597302166-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

생성물 1

HCID 444340826-(2-(3,3-dimethylbutyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
70 °C

실험 절차

Mix 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide (Example 447, Part E, 0.300 g, 1.06 mmol), K2CO3 (0.366 g, 2.65 mmol), and 1-bromo-3,3-dimethylbutane (0.183 g, 1.11 mmol) in DMF (5.3 mL). Heat at 70° C. overnight. Cool the reaction mixture to room temperature and add ethyl acetate (100 mL). Wash with water (1×30 mL) and brine (1×30 mL). Dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 6% to 15% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound : MS ES+368.2 (M+H)+, HRMS calcd for C22H30N3O2 368.2338 (M+H)+, found 368.2321, time 0.53 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18 min], tR=11.1 min, 96.8% purity.

후처리

  1. temperatureCool the reaction mixture to room temperature
  2. washWash with water (1×30 mL) and brine (1×30 mL)
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify by flash chromatography
  7. washeluting with 6% to 15% (2.0 M NH3 in methanol) in ethyl acetate

출처 및 근거

ORD 기록
ord-0a66d3d3bf894c478f849bd1c4185626
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07381719B2

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