Water → 5-Cyano-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amide

HRID 751710Notes

Reaction equation

HRID 751710 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)=[O:5].CC[N:23]([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25].C1C=C[C:33]2[N:38](O)N=[N:36][C:34]=2[CH:35]=1.[OH2:40].CCN=C=NCCCN(C)C>CN(C=O)C>[F:20][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][C@H:3]([NH:2][C:26]([C:24]2[NH:23][C:27]3=[CH:28][N:36]=[C:34]([C:33]#[N:38])[CH:35]=[C:29]3[CH:25]=2)=[O:40])[C:4]([N:6]2[CH2:7][CH2:8][CH:9]([OH:12])[CH2:10][CH2:11]2)=[O:5])=[CH:19][CH:18]=1

Participants

7

Reactant 5

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67278381(S)-2-Amino-3-(4-fluoro-phenyl)-1-(4-hydroxy-piperidin-1-yl)-propan-1-one hydrochloride

Product 1

HCID 111780515-Cyano-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(S)-amino-3-(4-fluorophenyl)-1-(4-hydroxypiperidin-1-yl)propan-1-one hydrochloride (Preparation 20, 0.036 g, 0.118 mmol) in DMF (anhydrous, 5 mL) was added DIPEA (0.061 mL, 0.353 mmol) then carboxylic acid (Preparation 62, 0.020 g, 0.107 mmol). To the stirred solution was added HOBt.H2O (0.016 g, 0.107 mmol) then, after 10 min, EDCI (0.025 g, 0.128 mmol). The reaction mixture was stirred for 18 h then all volatiles were removed in vacuo. The residue was partitioned between CH2Cl2 (30 mL) and water (20 mL). The layers were separated then the aqueous was extracted with CH2Cl2 (2×30 mL). The combined organics were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in methanol then adsorbed onto silica gel. Purification via flash column chromatography (SiO2, methanol:dichloromethane, 7:93, v/v) gave the title compound as a white solid. δH (d6 DMSO): 1.05–1.32 (2H, m), 1.49–1.72 (2H, m), 2.86–3.42 (4H, m), 3.53–3.87 (2.5H, m), 3.93–4.05 (0.5H, m), 4.69 (1H, d), 5.07–5.21 (1H, m), 6.97–7.12 (2H, m), 7.26–7.39 (2H, m), 7.47 (1H, s), 8.41 (1H, s), 8.81 (1H, s), 9.01–9.41 (1H, m), 12.64 (1H, s); m/z (ES+)=436 [M+H]+; RT=1.51 min.

Workup

  1. customall volatiles were removed in vacuo
  2. customThe residue was partitioned between CH2Cl2 (30 mL) and water (20 mL)
  3. customThe layers were separated
  4. extractionthe aqueous was extracted with CH2Cl2 (2×30 mL)
  5. washThe combined organics were washed with brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in methanol
  10. customPurification via flash column chromatography (SiO2, methanol

Sources & evidence

ORD record
ord-c3b181ce431143cf9df042c5783fd215
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

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