Sodium Sulfate → HCID 67464623, Verbindung

HRID 1476967Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1476967
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:15]2[C:16]([CH3:34])=[CH:17][N:18]([CH:31]([CH3:33])[CH3:32])[C:19]=2[CH:20]=[C:21]([C:23]2[CH:24]=[N:25][C:26]([CH:29]=O)=[CH:27][CH:28]=2)[CH:22]=1)=[O:13].[NH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1.S([O-])([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>C(Cl)Cl.CO>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:15]2[C:16]([CH3:34])=[CH:17][N:18]([CH:31]([CH3:33])[CH3:32])[C:19]=2[CH:20]=[C:21]([C:23]2[CH:24]=[N:25][C:26]([CH2:29][N:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)=[CH:27][CH:28]=2)[CH:22]=1)=[O:13]

Komponenten

7

Edukt 4

HCID 24436Sodium SulfateHCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 54670907N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(6-formylpyridin-3-yl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide

Produkt 1

HCID 67464623HCID 67464623, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

To a solution of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(6-formylpyridin-3-yl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (100 mg, 0.219 mmol), in DCM (10 mL) and methanol (2 mL) was added pyrrolidine (0.035 mL, 0.438 mmol), followed by sodium sulfate (31.1 mg, 0.219 mmol). The reaction stirred at rt for 12 h, at which time sodium borohydride (16.57 mg, 0.438 mmol) was added and the reaction stirred rt for 2 h and 45° C. for 2 h. The reaction was quenched with water and extracted with EtOAc. The organic layer was evaporated. Purification by reverse phase Gilson HPLC (10-60% acetonitrile/water+0.1% TFA, YMC ODS-A C18 Column 75×30 mm ID S-5 um, 12 nM Column 7 minutes), followed by isolation and extraction with EtOAc/0.1 N NaOH provided N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indole-4-carboxamide, which was evaporated from the organic layer as a yellow foam solid (68 mg, 0.125 mmol, 57.0% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.48 (br. s., 1H) 9.06 (d, J=2.02 Hz, 1H) 8.30 (dd, J=8.08, 2.27 Hz, 1H) 8.20 (t, J=5.18 Hz, 1H) 7.94 (d, J=1.26 Hz, 1H) 7.60 (d, J=8.08 Hz, 1H) 7.40 (s, 1H) 7.32 (s, 1H) 5.88 (s, 1H) 4.92-4.89 (m, 1H) 4.59 (d, J=5.56 Hz, 2H) 4.36 (d, J=5.05 Hz, 2H) 3.34 (br. s., 4H) 2.25 (s, 3H) 2.17 (d, J=1.01 Hz, 3H) 2.11 (s, 3H) 1.99 (br.s., 4H) 1.45 (d, J=6.57 Hz, 6H). LCMS: [M+H]+=512.3.

Aufarbeitung

  1. additionwas added
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. customThe organic layer was evaporated
  5. customPurification by reverse phase Gilson HPLC (10-60% acetonitrile/water+0.1% TFA, YMC ODS-A C18 Column 75×30 mm ID S-5 um, 12 nM Column 7 minutes)
  6. extractionfollowed by isolation and extraction with EtOAc/0.1 N NaOH

Quellen und Nachweise

ORD-Eintrag
ord-4ee17772231c43549c810718d2e596fa
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09402836B2

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