Triethylamine → N-((1R)-4-Amino-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}-4-oxobutyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide

HRID 1697812ノート

反応式

HRID 1697812 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([NH:14][C@@H:15]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[N:29]=[C:30]4[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][N:31]4[CH:37]=3)=[CH:24][CH:23]=2)[CH2:16][CH2:17][C:18]([OH:20])=O)=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C([N:40](CC)CC)C.ClC(OCC)=O>C1COCC1>[NH2:40][C:18](=[O:20])[CH2:17][CH2:16][C@@H:15]([NH:14][C:12](=[O:13])[C:4]1[CH:5]=[CH:6][C:7]([O:8][CH:9]([CH3:10])[CH3:11])=[C:2]([Cl:1])[CH:3]=1)[CH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[N:29]=[C:30]3[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][N:31]3[CH:37]=2)=[CH:26][CH:27]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 67278023HCID 67278023、化合物

生成物 1

HCID 57594405N-((1R)-4-Amino-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}-4-oxobutyl)-3-chloro-4-[(1-methylethyl)oxy]benzamide収率 90%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of (4R)-4-[({3-chloro-4-[(1-methylethyl)oxy]phenyl}carbonyl)amino]-5-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]pentanoic acid (900 mg, 1.73 mmol) in anhydrous THF (12.4 mL) at 0° C. under nitrogen was added triethylamine (242 uL, 1.73 mmol) followed by ethyl chloroformate (174 uL, 1.82 mmol). The reaction was stirred for 40 min at 0° C. and then the solids were filtered and washed with 5 mL THF. The filtrate was added to a flask containing NH4OH (5 mL) at room temperature and the reaction mixture was stirred for 1 hour. The product was extracted from the reaction mixture with EtOAc (50 mL). The aqueous layer was extracted with EtOAc (20 mL) and then acidified with 1N HCl solution (30 mL) and re-extracted with EtOAc (10 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to give a white solid. Purification by recrystallization from hot isopropanol afforded the title compound as a white solid (90%). ESMS [M+H]+=519.4.

後処理

  1. filtrationthe solids were filtered
  2. washwashed with 5 mL THF
  3. additionThe filtrate was added to a flask
  4. additioncontaining NH4OH (5 mL) at room temperature
  5. stirringthe reaction mixture was stirred for 1 hour
  6. extractionThe product was extracted from the reaction mixture with EtOAc (50 mL)
  7. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  8. extractionre-extracted with EtOAc (10 mL)
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customto give a white solid
  12. customPurification
  13. customby recrystallization from hot isopropanol

出典と根拠

ORDレコード
ord-60ef506e64824f3e9aff833b73806c8d
出典データセット
uspto-grants-2012_04
特許番号
US08163919B2

反応ノート

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