1-Hydroxybenzotriazole → 6-(2-dimethylamino-ethoxy)-1-isopropyl-1H-indole-4-carboxylic acid (6-methyl-2-oxo-4-propyl-1,2-dihydro-pyridin-3-ylmethyl)-amide

HRID 62322

Reaktionsgleichung

Reaktionsgleichung von HRID 62322
[CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:18]([OH:20])=O)[C:9]2[CH:10]=[CH:11][N:12]([CH:15]([CH3:17])[CH3:16])[C:13]=2[CH:14]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:53][CH2:54][C:55]1[C:56](=[O:65])[NH:57][C:58]([CH3:64])=[CH:59][C:60]=1[CH2:61][CH2:62][CH3:63]>CN(C=O)C.O>[CH3:64][C:58]1[NH:57][C:56](=[O:65])[C:55]([CH2:54][NH:53][C:18]([C:8]2[C:9]3[CH:10]=[CH:11][N:12]([CH:15]([CH3:16])[CH3:17])[C:13]=3[CH:14]=[C:6]([O:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:21])[CH:7]=2)=[O:20])=[C:60]([CH2:61][CH2:62][CH3:63])[CH:59]=1

Komponenten

8

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateHCID 674640256-(2-dimethylamino-ethoxy)-1-isopropyl-1H-indole-4-carboxylic acid

Produkt 1

HCID 546702686-(2-dimethylamino-ethoxy)-1-isopropyl-1H-indole-4-carboxylic acid (6-methyl-2-oxo-4-propyl-1,2-dihydro-pyridin-3-ylmethyl)-amideAusbeute 19,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a cooled (0° C.) mixture of 6-(2-dimethylamino-ethoxy)-1-isopropyl-1H-indole-4-carboxylic acid (400 mg, 1.37 mmol) in DMF (10 mL) was added EDC.HCl (310 mg, 1.65 mmol) and HOBt.H2O (250 mg, 1.65 mmol). The reaction was stirred for 15 min, then DIPEA (1.2 mL, 6.89 mmol) and 3-aminomethyl-6-methyl-4-propyl-1H-pyridin-2-one (240 mg, 1.37 mmol) were added. The reaction was allowed to warm to RT and stirred for 16 h, at which time it was diluted with water (20 mL) and extracted with DCM (2×15 mL). The combined DCM layer was dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography eluting with 3% MeOH in chloroform and then further purified by preparative HPLC to furnish 6-(2-dimethylamino-ethoxy)-1-isopropyl-1H-indole-4-carboxylic acid (6-methyl-2-oxo-4-propyl-1,2-dihydro-pyridin-3-ylmethyl)-amide (120 mg, 19%) as an off white solid. 1H NMR (400 MHz, DMSO-d6): δ 0.92-0.88 (t, 3H), 1.43-1.41 (d, J=6.8 Hz, 6H), 1.56 (m, 2H), 2.12 (s, 3H), 2.22 (s, 6H), 2.55-2.53 (m, 2H), 2.06 (m, 2H), 4.11-4.09 (t, 2H), 4.36-4.34 (d, J=4.8 Hz, 2H), 4.76-4.73 (m, 1H), 5.90 (s, 1H), 6.74-6.73 (d, J=2.8 Hz, 1H), 7.04 (s, 1H), 7.20 (s, 1H), 7.43-7.42 (d, J=3.2 Hz, 1H), 8.10-8.07 (bs, 1H), 11.55 (bs, 1H). LCMS (ES+): m/z=453.23[M+H].

Aufarbeitung

  1. temperatureTo a cooled
  2. stirringstirred for 16 h, at which time it
  3. extractionextracted with DCM (2×15 mL)
  4. dry with materialThe combined DCM layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography
  7. washeluting with 3% MeOH in chloroform
  8. customfurther purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-1ae71f0aaad648fc83e6f6fb07569abb
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09446041B2

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