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 1693421Notes

Reaction equation

HRID 1693421 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-c21f9a0c913346d791adf277e73f09e7
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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