1-Hydroxybenzotriazole → 1-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid methyl-(4-methyl-benzyl)-amide

HRID 408597

反応式

HRID 408597 の反応式
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:12]2[CH2:15][CH2:14][C:13]2([CH3:19])[C:16]([OH:18])=O)=[O:11])[CH:5]=[C:6]([CH3:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH3:42][NH:43][CH2:44][C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=1>CN(C=O)C.C1COCC1.C(Cl)Cl>[CH3:42][N:43]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=1)[C:16]([C:13]1([CH3:19])[CH2:14][CH2:15][N:12]1[C:10](=[O:11])[CH2:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[CH:3]=1)=[O:18]

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2794640N-Methyl-4-methylbenzylamineHCID 705580721-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid

生成物 1

HCID 705573251-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid methyl-(4-methyl-benzyl)-amide

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
20 °C

実験手順

To a solution of Intermediate 119 1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid (1 eq.) in either DCM, THF or DMF was added HOBt (1.1 eq.), EDC.HCl (1.5 eq.), TEA (3 eq.) and methyl-(4-methyl benzyl)-amine (1.5 eq.). The reaction was stirred at 20° C. for 15 h, then the crude was concentrated under reduced pressure and partitioned between a saturated aqueous solution of NaHCO3 and EtOAc. The aqueous layer was extracted three times with EtOAc. The organic layers were combined, washed with water then with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with DCM/MeOH: 100/0 to 99/1) to afford 1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid methyl-(4-methyl-benzyl)-amide.

後処理

  1. concentrationthe crude was concentrated under reduced pressure
  2. custompartitioned between a saturated aqueous solution of NaHCO3 and EtOAc
  3. extractionThe aqueous layer was extracted three times with EtOAc
  4. washwashed with water
  5. dry with materialwith brine, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified by chromatography on silica gel (elution with DCM/MeOH: 100/0 to 99/1)

出典と根拠

ORDレコード
ord-269bd3c177f04cafbeeca40885a0f210
出典データセット
uspto-grants-2014_06
特許番号
US08759334B2

関連ノート

読み込み中…