4-Bromophenyl isothiocyanate → Tert-butyl 4-{2-[(4-bromophenyl)amino]-1-methylbenzimidazol-5-yloxy}pyridine-2-carboxylate

HRID 1915625ノート

反応式

HRID 1915625 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[NH:22][CH3:23])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:7]=1.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]=[C:32]=S)=[CH:27][CH:26]=1.Cl.C(N=C=NCCCN(C)C)C>O1CCCC1>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]2[N:22]([CH3:23])[C:21]3[CH:20]=[CH:19][C:4]([O:5][C:6]4[CH:11]=[CH:10][N:9]=[C:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:7]=4)=[CH:3][C:2]=3[N:1]=2)=[CH:27][CH:26]=1

参加物

5

反応物 3

HCID 161334-Bromophenyl isothiocyanateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22040526Tert-butyl4-[3-amino-4-(methylamino)phenoxy]pyridine-2-carboxylate

生成物 1

HCID 22041284Tert-butyl 4-{2-[(4-bromophenyl)amino]-1-methylbenzimidazol-5-yloxy}pyridine-2-carboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

A solution of the diamine from step 6 (1 eq) and 4-bromophenyl isothiocyanate (1 eq) in anhydrous tetrahydrofuran under nitrogen was stirred at 20° C. for 2-3 hours or when determined to be complete by HPLC. The solution was treated with 3 equivalents of 1-ethyl-(3-dimethylaminopropyl)carbodiimide HCl. The stirred solution was heated to 50° C. under nitrogen for 2-3 hrs or until the reaction is determined to be complete by HPLC. The reaction was evaporated under reduced pressure and then diluted with ethyl acetate and water. The aqueous layer was back extracted with ethyl acetate. The combined organic layers were washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and later evaporated under reduced pressure. The crude material was purified by reverse high-pressure liquid chromatography to afford the product as a brown powder after lyophlization. MS: MH+=495.

後処理

  1. customThe reaction was evaporated under reduced pressure
  2. additiondiluted with ethyl acetate and water
  3. extractionThe aqueous layer was back extracted with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customlater evaporated under reduced pressure
  7. customThe crude material was purified

出典と根拠

ORDレコード
ord-20bdc7ce0b41426bb087250da702ffcf
出典データセット
uspto-grants-2013_12
特許番号
US08614330B2

反応ノート

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