Potassium Hydroxide → (1S,3R)-3-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)cyclopentanecarboxylic acid

HRID 1963932ノート

反応式

HRID 1963932 の反応式
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[NH2:24][C@@H:25]1[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26]1.[OH-].[K+]>O1CCOCC1>[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:24][C@@H:25]2[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26]2)=[N:6][CH:7]=1

参加物

5

反応物 3

HCID 14797Potassium HydroxideHCID 15020343-Aminocyclopentane-1-carboxylic acidHCID 58127193HCID 58127193、化合物

生成物 1

HCID 66936933(1S,3R)-3-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)cyclopentanecarboxylic acid収率 7.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine (100 mg, 0.301 mmol), was added (1S,3R)-3-aminocyclopentanecarboxylic acid (117 mg, 0.904 mmol), powdered potassium hydroxide (85 mg, 1.507 mmol) and dioxane (1 ml). The reaction mixture was stirred at 100° C. for 18 hr in a sealed vessel and followed by LCMS. The crude reaction mixture was partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate. The organic layer was removed, dried over sodium sulfate, and reduced. This was redissolved in 1.5 mL DMSO, filtered, and purified through prep LC. The product fractions were combined and extracted with 50 mL ethyl acetate, which was dried over sodium sulfate, and concentrated to constant mass. 10 mg of the desired compound was obtained. LCMS (m/z): 441.2 (MH+), retention time=0.68 min. 1H NMR (400 MHz, CHLOROFORM-d, 25° C.) δ ppm 1.59 (m, 2 H) 1.83 (m, 2 H) 1.99 (m, 1 H) 2.72 (m, 1 H) 3.40 (br. s., 1 H) 3.78 (br. s., 1 H) 4.42 (br. s., 1 H) 5.48 (br. s., 1 H) 6.29 (d, J=8.22 Hz, 1 H) 6.50 (s, 1 H) 6.80-6.92 (m, 2 H) 6.95-7.10 (m, 2 H) 7.16-7.25 (m, 1 H) 7.38 (t, J=8.02 Hz, 1 H) 7.89 (s, 1 H).

後処理

  1. customThe crude reaction mixture
  2. customwas partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate
  3. customThe organic layer was removed
  4. dry with materialdried over sodium sulfate
  5. dissolutionThis was redissolved in 1.5 mL DMSO
  6. filtrationfiltered
  7. custompurified through prep LC
  8. extractionextracted with 50 mL ethyl acetate, which
  9. dry with materialwas dried over sodium sulfate
  10. concentrationconcentrated to constant mass

出典と根拠

ORDレコード
ord-664e27df708347c48642e95571410d12
出典データセット
uspto-grants-2013_04
特許番号
US08415381B2

反応ノート

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