Potassium Carbonate → N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-methoxypyridin-3-yl)-5-chloropicolinamide

HRID 930384ノート

反応式

HRID 930384 の反応式
Br[C:2]1[CH:3]=[C:4]([C@:10]2([CH3:21])[CH2:15][C@@H:14]([C:16]([F:19])([F:18])[F:17])[O:13][C:12]([NH2:20])=[N:11]2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]([NH2:31])=[O:30])=[N:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.O1CCOCC1>[NH2:20][C:12]1[O:13][C@H:14]([C:16]([F:19])([F:18])[F:17])[CH2:15][C@:10]([C:4]2[CH:3]=[C:2]([NH:31][C:29](=[O:30])[C:26]3[CH:25]=[CH:24][C:23]([Cl:22])=[CH:28][N:27]=3)[CH:7]=[N:6][C:5]=2[O:8][CH3:9])([CH3:21])[N:11]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 218831585-Chloropyridine-2-carboxamideHCID 86732212(4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

生成物 1

HCID 86732213N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-methoxypyridin-3-yl)-5-chloropicolinamide収率 24.06%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A microwave vial was charged with (4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.100 g, 0.272 mmol), 5-chloropicolinamide (0.064 g, 0.407 mmol), copper(I) iodide (10.35 mg, 0.054 mmol) and potassium carbonate powder (0.113 g, 0.815 mmol). The vial was purged with nitrogen followed by the addition of 1,4-dioxane 1 mL and (1R,2R)-(−)-N,N″-dimethylcyclohexane-1,2-diamine (0.043 ml, 0.272 mmol). The vial was sealed and heated at 120° C. overnight. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc three times. The organic layers were combined, washed with brine and dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using a gradient of 15-85% EtOAc/hexane to give N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-methoxypyridin-3-yl)-5-chloropicolinamide (0.029 g, 0.065 mmol, 24.06% yield). MS m/z=443.9 [M+H]+. Calculated for C18H17ClF3N5O3: 443.8

後処理

  1. customThe vial was purged with nitrogen
  2. customThe vial was sealed
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. extractionThe aqueous layer was extracted with EtOAc three times
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography

出典と根拠

ORDレコード
ord-14ee33f092574c27a09c3c333f363750
出典データセット
uspto-grants-2016_03
特許番号
US09296734B2

反応ノート

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