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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(tert-butyldimethylsilanyloxymethyl)-2-(S)-hydroxy-2-phenylethyl]amide

HRID 1693408
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HRID 1693408 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[NH:8][C:5]2=[CH:6][N:7]=1.[NH2:14][CH:15]([CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[OH:17].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C.[Cl-].[Na+].O>[Si:26]([O:25][CH2:24][C@H:15]([NH:14][C:11]([C:9]1[NH:8][C:5]2=[CH:6][N:7]=[C:2]([Cl:1])[CH:3]=[C:4]2[CH:10]=1)=[O:13])[C@@H:16]([OH:17])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]
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참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 147318252-Amino-3-(tert-butyldimethylsilanyloxy)-1-phenylpropan-1-olHCID 446307045-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

생성물 1

HCID 57550106
5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(tert-butyldimethylsilanyloxymethyl)-2-(S)-hydroxy-2-phenylethyl]amide

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 57417360Sodium chloride; water용매

실험 절차

To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18, 520 mg, 2.65 mmol) and 2-amino-3-(tert-butyldimethylsilanyloxy)-1-phenylpropan-1-ol (Preparation 99, 780 mg, 2.77 mmol) in DMF (15 mL) was added HOBt (411 mg, 2.68 mmol), DIPEA (0.96 mL, 5.51 mmol) and EDCI (589 mg, 3.07 mmol). After stirring at rt for 12 h the mixture was added to diluted brine (150 mL, water/brine: 1/1). Extraction with ethyl acetate (4×50 mL), washing of the combined extracts with diluted hydrochloric acid (1M, 50 ml), diluted aqueous sodium hydroxide solution (1M, 50 ml) and brine (50 mL) followed by drying (MgSO4) gave after concentration a residue which was purified by flash chromatography on silica gel (eluent: hexane/ethyl acetate: 50/50). The title compound was obtained as colourless oil. δH (CD3OD): 0.00, 0.01 (6H, 2s), 0.84 (9H, s), 3.60 (1H, dd), 3.84 (1H, dd), 4.33 (1H, ddd), 4.98 (1H, d), 7.05 (1H, s), 7.12-7.37 (5H, 3m), 7.60 (1H, s), 8.49 (1H, s); m/z (ES+)=460.36 [M+H]+; RT=4.16 min.

후처리

  1. extractionExtraction with ethyl acetate (4×50 mL)
  2. washwashing of the combined extracts with diluted hydrochloric acid (1M, 50 ml), diluted aqueous sodium hydroxide solution (1M, 50 ml) and brine (50 mL)
  3. dry with materialby drying (MgSO4)
  4. customgave
  5. concentrationafter concentration a residue which
  6. customwas purified by flash chromatography on silica gel (eluent: hexane/ethyl acetate: 50/50)

출처 및 근거

ORD 기록
ord-d6d3d54640d140399e8e8d874cc3dda1
출처 데이터셋
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08158622B2

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