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

HRID 474148ノート

反応式

HRID 474148 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 75806Tricyclohexylphosphine触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-39255b7e875d42ffaaf1c0a9a35d89ba
出典データセット
uspto-grants-2014_01
特許番号
US08637513B2

反応ノート

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