Potassium Phosphate, Tribasic → 2-[4-(3-methylpyrazin-2-yl)phenyl]-N-[(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl]acetamide

HRID 474148노트

반응식

HRID 474148 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:18][C@@H:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]([F:32])([F:31])[F:30])=[CH:23][N:22]=3)[CH3:20])=[O:17])=[CH:11][CH:10]=2)O1.Cl[C:35]1[C:40]([CH3:41])=[N:39][CH:38]=[CH:37][N:36]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH3:41][C:40]1[C:35]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:18][C@@H:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]([F:31])([F:32])[F:30])=[CH:23][N:22]=3)[CH3:20])=[O:17])=[CH:11][CH:10]=2)=[N:36][CH:37]=[CH:38][N:39]=1

참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 66769Pyrazine, 2-chloro-3-methyl-HCID 684960762-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

생성물 1

HCID 426099622-[4-(3-methylpyrazin-2-yl)phenyl]-N-[(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl]acetamide수율 73.5%

시약·촉매·용매 3

HCID 75806Tricyclohexylphosphine촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

To a solution of 1.00 g (2.15 mmol) 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide in 5.70 ml dioxane was added 0.31 g (2.58 mmol) 2-chloro-3-methylpyrazine, 0.014 mg (0.052 mmol) tricyclohexylphosphine, 0.020 g (0.022 mmol) Pd2dba3, and 2.88 mL (3.66 mmol) 1.7M potassium phosphate. The resulting suspension was degassed for 10mins. After 30 min in the microwave at 150° C., the reaction mixture was cooled, extracted with ethyl acetate, and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 30-100% EtOAc:hexane) followed by purification by reverse phase chromatography afforded 0.68 g (73.3%) 2-[4-(3-methylpyrazin-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide. 1H NMR (CDCl3, 400 MHz) 8.49 (d, 1H, J=2.20 Hz); 8.45 (d, 1H, J=2.38 Hz); 8.21 (d, 1H, J=2.39 Hz); 7.57 (d, 2H, J=8.24 Hz); 7.41 (d, 2H, J=7.83 Hz); 7.24-7.17 (m, 2H); 6.73 (br d, 1H, J=7.33 Hz); 5.13 (m, 1H); 4.38 (q, 2H, J=8.05 Hz); 3.67 (s, 2H); 2.65 (s, 3H); 1.41 (d, 3H, J=6.77). FIRMS (ES) exact mass calcd for C22H21F3N4O2: 431.1689, Found: 431.1690. FLIPR alpha1I IP=24 nM.

후처리

  1. customThe resulting suspension was degassed for 10mins
  2. temperaturethe reaction mixture was cooled
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over NaSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (silica gel, linear gradient 30-100% EtOAc:hexane)
  9. customfollowed by purification by reverse phase chromatography

출처 및 근거

ORD 기록
ord-39255b7e875d42ffaaf1c0a9a35d89ba
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637513B2

반응 노트

불러오는 중…