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Diisopropylethylamine → N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester

HRID 393064
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HRID 393064 반응식
C(N(C(C)C)CC)(C)C.Cl.[CH3:11][O:12][C:13](=[O:25])[C@H:14]([CH2:16][NH:17][C:18]([C:20]1[S:21][CH:22]=[CH:23][CH:24]=1)=[O:19])[NH2:15].[Cl:26][C:27]1[CH:35]=[C:34]([C:36]([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([OH:46])[CH:41]=2)=[O:37])[CH:33]=[CH:32][C:28]=1[C:29](O)=[O:30].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:26][C:27]1[CH:35]=[C:34]([C:36]([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([OH:46])[CH:41]=2)=[O:37])[CH:33]=[CH:32][C:28]=1[C:29]([NH:15][C@H:14]([C:13]([O:12][CH3:11])=[O:25])[CH2:16][NH:17][C:18]([C:20]1[S:21][CH:22]=[CH:23][CH:24]=1)=[O:19])=[O:30]
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 226613972-Chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acidHCID 688207093-(thiophene-2-carbonyl)amino-L-alanine methyl ester hydrochloride

생성물 1

HCID 131723032
N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester
수율 70.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Diisopropylethylamine (7.00 g, 64.2 mmol) was added to a solution of 3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester hydrochloride (Example 301; 7.00 g, 26.4 mmol), 2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoic acid (Example 26; 7.00 g, 22.9 mmol), and HBTU (13.00 g, 34.3 mmol) in DMF (75 mL). The solution was allowed to stir at room temperature for 4 days, and it was then concentrated to remove most of the DMF. Ethyl acetate (200 mL) was added, followed by water (200 mL) and 1 M HCl (100 mL). The layers were separated; the ethyl acetate layer was evaporated, and the residue was chromatographed (50-100% ethyl acetate/hexanes) to give N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine, methyl ester (8.30 g, 70%) as a white solid.

후처리

  1. concentrationit was then concentrated
  2. customto remove most of the DMF
  3. additionEthyl acetate (200 mL) was added
  4. customThe layers were separated
  5. customthe ethyl acetate layer was evaporated
  6. customthe residue was chromatographed (50-100% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-ad4df8bf638f4b308cc3f7c66556a089
출처 데이터셋
uspto-grants-2004_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06803384B2

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