Diisopropylethylamine → 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]sulfonyl]phenyl]carbonyl]-L-phenylalanine methyl ester

HRID 1976959ノート

反応式

HRID 1976959 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]([S:11]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)(=[O:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:23][O:24][C:25](=[O:46])[C@H:26]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36]([C:38]2[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=2[Cl:45])=[O:37])=[CH:31][CH:30]=1)[NH2:27].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O>[CH3:23][O:24][C:25](=[O:46])[C@H:26]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([NH:35][C:36]([C:38]2[C:43]([Cl:44])=[CH:42][CH:41]=[CH:40][C:39]=2[Cl:45])=[O:37])=[CH:33][CH:34]=1)[NH:27][C:4]([C:3]1[CH:7]=[CH:8][C:9]([S:11]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)(=[O:13])=[O:12])=[CH:10][C:2]=1[Cl:1])=[O:6]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 219993292-Chloro-4-[(3-hydroxybenzylamino)sulfonyl]benzoic acidHCID 233839334-(2,6-Dichlorobenzoylamino)-L-phenylalanine methyl ester

生成物 1

HCID 541912724-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]sulfonyl]phenyl]carbonyl]-L-phenylalanine methyl ester収率 54.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of 2-chloro-4-[(3-hydroxybenzylamino)sulfonyl]benzoic acid (50 mg; 0.146 mmol), 4-[[(2,6-dichlorophenyl)carbonyl]amino]-L-phenylalanine methyl ester (60 mg; 0.1486 mmol), HBTU (5 mg; 0.15 mmol) and DIPEA (0.102 mL; 0.585 mmol) in dimethylformamide (3 mL) was stirred for 17 hr under argon at room temperature, then was concentrated to dryness under reduced pressure. The residue was partitioned between dichloromethane (25 mL) and 0.5 N HCl (25 mL). The separated aqueous phase was re-extracted with dichloromethane (10 mL), then the organic extacts were washed in turn with water (2×25 mL). The combined dichloromethane layers were dried (Na2SO4) and evaporated to give 90 mg of the crude product as a dark oil. Chromatography of the oil over silica gel (9 g; 4:1 ethyl acetate-hexane) yielded 55 mg of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]sulfonyl]phenyl]carbonyl]-L-phenylalanine methyl ester, as a colorless solid. FAB HRMS: (C31H26Cl3N3O7S) Obs. Mass 690.0639 Calcd. Mass 690.0635 (M+H).

後処理

  1. concentrationwas concentrated to dryness under reduced pressure
  2. customThe residue was partitioned between dichloromethane (25 mL) and 0.5 N HCl (25 mL)
  3. extractionThe separated aqueous phase was re-extracted with dichloromethane (10 mL)
  4. washthe organic extacts were washed in turn with water (2×25 mL)
  5. dry with materialThe combined dichloromethane layers were dried (Na2SO4)
  6. customevaporated
  7. customto give 90 mg of the crude product as a dark oil

出典と根拠

ORDレコード
ord-a517b86567e34ff79cf42e4628d53603
出典データセット
uspto-grants-2001_05
特許番号
US06229011B1

反応ノート

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