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 751663Notes

Reaction equation

HRID 751663 reaction equation
[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]

Participants

8

Reactant 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

Product 1

HCID 575501065-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(tert-butyldimethylsilanyloxymethyl)-2-(S)-hydroxy-2-phenylethyl]amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

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 (11H, s); m/z (ES+)=460.36 [M+H]+; RT=4.16 min.

Workup

  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)

Sources & evidence

ORD record
ord-698d08e42c2d47f697ca05ccfad05f15
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

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