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 751710노트

반응식

HRID 751710 반응식
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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c3b181ce431143cf9df042c5783fd215
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07405210B2

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