1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-benzyl-3-(cis-3,4-dihydroxypyrrolidine-1-yl)-2(R)-hydroxy-3-oxopropyl]amide

HRID 751676Notes

Reaction equation

HRID 751676 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@@H:15]([OH:19])[C:16](O)=[O:17])=[O:12])[NH:8][C:5]2=[CH:6][N:7]=1.[OH:27][C@H:28]1[C@@H:32]([OH:33])[CH2:31][NH:30][CH2:29]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[CH2:20]([C@H:14]([NH:13][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:12])[C@@H:15]([OH:19])[C:16]([N:30]1[CH2:31][C@H:32]([OH:33])[C@H:28]([OH:27])[CH2:29]1)=[O:17])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13329882(3R,4S)-pyrrolidine-3,4-diolHCID 59753553(S)-3-[(5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-(R)-2-hydroxy-4-phenylbutyric acid

Product 1

HCID 113401055-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-benzyl-3-(cis-3,4-dihydroxypyrrolidine-1-yl)-2(R)-hydroxy-3-oxopropyl]amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-3-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-2-(R)-hydroxy-4-phenylbutyric acid (EXAMPLE 44, 50 mg, 0.13 mmol), cis-3,4-dihydroxypyrrolidine (Preparation 23, 15 mg, 0.15 mmol) and HOBt (27 mg, 0.20 mmol) in DMF (5 mL), was added DIPEA (47 μL, 0.27 mmol). After stirring for 5 min, EDCI (28 mg, 0.15 mmol) was added and the reaction stirred at rt for 72 h. The solvent was removed in vacuo and the residue partitioned between water (30 mL) and ethyl acetate (3×30 mL). The combined organic fractions were dried (MgSO4), concentrated in vacuo and the residue purified by chromatography on silica gel eluting with methanol/dichloromethane (1:9) to give the title compound as a white solid. m/z (ES+)=459 [M+H]+. RT=3.07 min.

Workup

  1. stirringthe reaction stirred at rt for 72 h
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between water (30 mL) and ethyl acetate (3×30 mL)
  4. dry with materialThe combined organic fractions were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customthe residue purified by chromatography on silica gel eluting with methanol/dichloromethane (1:9)

Sources & evidence

ORD record
ord-8e8e628b5e3f46b1885267658cb97614
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

Loading…