1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid [1-(S)-(4-fluoro-benzyl)-2-(3-hydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide

HRID 1693489Notes

Reaction equation

HRID 1693489 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:15](O)=[O:16])=[O:12])[NH:8][C:5]2=[N:6][CH:7]=1.[OH:26][C@@H:27]1[CH2:31][CH2:30][NH:29][CH2:28]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[F:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][C@H:14]([NH:13][C:11]([C:9]2[NH:8][C:5]3=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=[C:4]3[CH:10]=2)=[O:12])[C:15]([N:29]2[CH2:30][CH2:31][CH:27]([OH:26])[CH2:28]2)=[O:16])=[CH:24][CH:23]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2759337(R)-3-PyrrolidinolHCID 597536772-(S)-[(5-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)-propionic acid

Product 1

HCID 672794245-Chloro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid [1-(S)-(4-fluoro-benzyl)-2-(3-hydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(S)-[(5-chloro-1H-pyrrolo[2,3-b]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 286, 30 mg, 0.08 mmol) in DMF (3 mL) was added (R)-(+)-3-hydroxypyrrolidine (7.2 mg, 0.08 mmol), HOBt (11.2 mg, 0.08 mmol) and DIPEA (30.3 μL, 0.17 mmol). After 5 min, EDCI (20.7 mg, 0.11 mmol) was added and the reaction was stirred at rt for 16 h. The solvent was removed in vacuo and the residue partitioned between water (20 mL) and ethyl acetate (3×20 mL). The combined organic fractions were washed with 2N sodium hydroxide solution (20 mL), brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was triturated from methanol to give the title compound. m/z (ES+)=431 [M+H]+; RT=3.44 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between water (20 mL) and ethyl acetate (3×20 mL)
  3. washThe combined organic fractions were washed with 2N sodium hydroxide solution (20 mL), brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was triturated from methanol

Sources & evidence

ORD record
ord-ce69d348355b4d6cbf6bc1381a696162
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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