4-Methylmorpholine → Z-Lys(Z)-Leu-Leu-OMe

HRID 849694ノート

反応式

HRID 849694 の反応式
CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.[NH2:18][C@H:19]([C:24]([NH:26][C@H:27]([C:32]([O:34][CH3:35])=[O:33])[CH2:28][CH:29]([CH3:31])[CH3:30])=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22].Cl.[NH:37]([C:57]([O:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)=[O:58])[C@H:38]([C:54](O)=[O:55])[CH2:39][CH2:40][CH2:41][CH2:42][NH:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45].C1CCC(N=C=NC2CCCCC2)CC1>C(OCC)(=O)C.CN(C=O)C>[NH:37]([C:57]([O:59][CH2:60][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=1)=[O:58])[C@H:38]([C:54]([NH:18][C@H:19]([C:24]([NH:26][C@H:27]([C:32]([O:34][CH3:35])=[O:33])[CH2:28][CH:29]([CH3:30])[CH3:31])=[O:25])[CH2:20][CH:21]([CH3:22])[CH3:23])=[O:55])[CH2:39][CH2:40][CH2:41][CH2:42][NH:43][C:44]([O:46][CH2:47][C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1)=[O:45]

参加物

8

反応物 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7269422N2,N6-Bis[(phenylmethoxy)carbonyl]-L-lysineHCID 15598024L-Leucine, L-leucyl-, methyl ester, hydrochloride (1:1)

生成物 1

HCID 12020551Z-Lys(Z)-Leu-Leu-OMe収率 99.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
19 °C

実験手順

4-Methylmorpholine (1.26 g, 12.5 mmol) and HOBt (1.69 g, 12.5 mmol) were added to a solution of H-Leu-Leu-OMe·HCl (4.04 g, 13.75 mmol) in ethyl acetate (160.0 g) and DMF (36.0 g) over 15 min. Z-Lys(Z)-OH (5.18 g, 12.5 mmol) was added to this stirred mixture over 15 min. A solution of DCC (3.10 g, 12.5 mmol) in ethyl acetate (10.0 g) was added dropwise at 18-20° C. over 30 min. The reaction mixture was stirred at 18-20° C. for 16 h and filtered. The filter cake was washed with ethyl acetate (100.0 g) and the combined filtrate was washed with aqueous NaHCO3. The resulting organic layer was washed with aqueous NaCl and concentrated under reduced pressure. The residue was dissolved in MeOH (80.0 g) at about 50° C. Water (160 g) was slowly added and the mixture was stirred for about 1 h at 20° C. The resulting solid was filtered, washed with H2O (80.0 g) and dried at 40° C. in a vacuum oven to give 8.16 g, 99.6% of the product Z-Lys(Z)-Leu-Leu-OMe.

後処理

  1. filtrationfiltered
  2. washThe filter cake was washed with ethyl acetate (100.0 g)
  3. washthe combined filtrate was washed with aqueous NaHCO3
  4. washThe resulting organic layer was washed with aqueous NaCl
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in MeOH (80.0 g) at about 50° C
  7. additionWater (160 g) was slowly added
  8. stirringthe mixture was stirred for about 1 h at 20° C
  9. filtrationThe resulting solid was filtered
  10. washwashed with H2O (80.0 g)
  11. customdried at 40° C. in a vacuum oven

出典と根拠

ORDレコード
ord-8dba8592b39c4c75b361172b82f4951b
出典データセット
uspto-grants-2000_01
特許番号
US06013764

反応ノート

読み込み中…