1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-3-[(5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-(R)-2-hydroxy-4-phenylbutyric acid methyl ester

HRID 1693445Notes

Reaction equation

HRID 1693445 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.[CH3:14][O:15][C:16](=[O:28])[C@H:17]([OH:27])[C@@H:18]([NH2:26])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[CH3:14][O:15][C:16](=[O:28])[C@H:17]([OH:27])[C@@H:18]([NH:26][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])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 118166163-Amino-2-hydroxy-4-phenyl-butyric acid methyl esterHCID 446307045-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid

Product 1

HCID 59753593(S)-3-[(5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-(R)-2-hydroxy-4-phenylbutyric acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18, 165 mg, 0.84 mmol) and (3S,2R)-3-amino-2-hydroxy-4-phenylbutyric acid methyl ester (Preparation 21, 175 mg, 0.84 mmol) in DMF (10 mL) was added HOBt (125 mg, 0.92 mmol), DIPEA (0.29 mL, 1.68 mmol) and EDCI (177 mg, 0.92 mmol) and the reaction stirred at rt for 72 h. The reaction solvent was removed in vacuo, and the residue partitioned between water (40 mL) and ethyl acetate (3×40 mL). The combined organic fractions were dried (MgSO4), concentrated in vacuo and the residue purified by chromatography on silica gel eluting with methanol/dichloromethane (3:97) to give the title compound as a yellow solid. δH (CD3OD): 2.97-3.12 (2H, m), 3.67 (1H, s), 4.25 (1H, d), 4.70-4.75 (1H, m), 7.08 (1H, s), 7.15-7.21 (1H, m), 7.25-7.34 (4H, m), 7.65 (1H, s), 8.55 (1H, s); m/z (ES+)=388 [M+H]+.

Workup

  1. customThe reaction solvent was removed in vacuo
  2. customthe residue partitioned between water (40 mL) and ethyl acetate (3×40 mL)
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customthe residue purified by chromatography on silica gel eluting with methanol/dichloromethane (3:97)

Sources & evidence

ORD record
ord-0fd33428ad7942be9bb4b1e12391f4d5
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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