4-Methylmorpholine → N-[1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidyl]-L-alanine 1,1-dimethylethyl ester

HRID 34491ノート

反応式

HRID 34491 の反応式
[Cl:1][C:2]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:22]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])=[O:23])[CH2:3][N:4]1[CH:21]=[N:20][C:6]([CH2:7][C@@H:8]([C:17]([OH:19])=O)[NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:5]1.CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.[CH3:57][C:58]([O:61][C:62](=[O:66])[C@H:63]([CH3:65])[NH2:64])([CH3:60])[CH3:59].Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:57][C:58]([O:61][C:62](=[O:66])[C@H:63]([CH3:65])[NH:64][C:17](=[O:19])[C@H:8]([CH2:7][C:6]1[N:20]=[CH:21][N:4]([CH2:3][C:2]([Cl:1])([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:22]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])=[O:23])[CH:5]=1)[NH:9][C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])([CH3:60])[CH3:59]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11275390tert-Butyl alaninate hydrochlorideHCID 228392281-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidine

生成物 1

HCID 14211453N-[1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidyl]-L-alanine 1,1-dimethylethyl ester収率 89.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred mixture of 1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidine (1.14 g), N-methylmorpholine (461 μl), 1-hydroxybenzotriazole hydrate (277 mg) and L-alanine 1,1-dimethylethyl ester hydrochloride (364 mg) in dichloromethane (30 ml) was added N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (422 mg). The resulting mixture was stirred for 18 hours, and concentrated under reduced pressure to yield a residue which was partitioned between ethyl acetate and water. The organic phase was washed with saturated aqueous sodium hydrogen carbonate and then brine and dried over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to yield a foam which was chromatographed on silica gel eluting with methanol/dichloromethane (1:24) to yield N-[1-[2-chloro-3-(2,4-dichlorophenyl)-3-oxo-2-phenylpropyl]-N-[(1,1-dimethylethoxy)carbonyl]-L-histidyl]-L-alanine 1,1-dimethylethyl ester as a white foam (1.25 g), and as a mixture of diastereoisomers, m.p. 85-90° C. (decomp), (Found: C, 55.57; H, 5.51; N, 7.86%; C33H39Cl3N4O6.H2O requires C, 55.66; H, 5.80; N, 7.87%), having the formula: ##STR35##

後処理

  1. concentrationconcentrated under reduced pressure
  2. customto yield a residue which
  3. customwas partitioned between ethyl acetate and water
  4. washThe organic phase was washed with saturated aqueous sodium hydrogen carbonate
  5. dry with materialbrine and dried over anhydrous magnesium sulphate
  6. customThe solvent was removed under reduced pressure
  7. customto yield a foam which
  8. customwas chromatographed on silica gel eluting with methanol/dichloromethane (1:24)

出典と根拠

ORDレコード
ord-99d8bdbf181a4420bdc4c25e5c95cbb4
出典データセット
uspto-grants-1988_08
特許番号
US04761483

反応ノート

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