ChemicalBook CAS DataBase List 1H-Indole-4-carboxaMide, 6-broMo-N-[(1,2-dihydro-4,6-diMethyl-2-oxo-3-pyridinyl)Methyl]-3-Methyl-1-[(1S)-1-Methylpropyl]-

1H-Indole-4-carboxaMide, 6-broMo-N-[(1,2-dihydro-4,6-diMethyl-2-oxo-3-pyridinyl)Methyl]-3-Methyl-1-[(1S)-1-Methylpropyl]- synthesis

8synthesis methods

Product Name:1H-Indole-4-carboxaMide, 6-broMo-N-[(1,2-dihydro-4,6-diMethyl-2-oxo-3-pyridinyl)Methyl]-3-Methyl-1-[(1S)-1-Methylpropyl]-
CAS Number:1346574-54-6
Molecular formula:C22H26BrN3O2
Molecular Weight:444.36

1346574-53-5 Synthesis

1H-Indole-4-carboxaMide,6-broMo-N-[(1,2-dihydro-4,6-diMethyl-2-oxo-3-pyridinyl)Methyl]-3-Methyl-1-(1-Methylpropyl)-

1346574-53-5
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1H-Indole-4-carboxaMide, 6-broMo-N-[(1,2-dihydro-4,6-diMethyl-2-oxo-3-pyridinyl)Methyl]-3-Methyl-1-[(1R)-1-Methylpropyl]-

1346574-55-7
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1H-Indole-4-carboxaMide, 6-broMo-N-[(1,2-dihydro-4,6-diMethyl-2-oxo-3-pyridinyl)Methyl]-3-Methyl-1-[(1S)-1-Methylpropyl]-

1346574-54-6
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Yield:1346574-54-6 901 mg ，1346574-55-7 856 mg

Reaction Conditions:

with Chiralpak AD-H in ethanol;n-heptane;Resolution of racemate;

Steps:

267; 268 (S)-6-bromo-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-1H-indole-4-carboxamide (Ex 267) and (R)-6-Bromo-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-1H-indole-4-carboxamide (Ex 268)

6-Bromo-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-1H-indole-4-carboxamide (racemic mixture, 1.9 g) was resolved by chiral HPLC (column: Chiralpak AD-H, 5 microns, 50 mm×250 mm, UV detection: 240 nM, flow rate: 100 mL/min, T=20 deg C., eluent: 60:40:0.1 n-heptane:ethanol:isopropylamine (isocratic)). For each run, 100 mg of the racemic compound was dissolved in 30 volumes (3.0 mL) of warm ethanol with a few drops of isopropylamine added. A total of 19 runs were performed. Baseline resolution was observed for each run. The isomer that eluted at 8.3-10.1 min was collected (following concentration) as a white solid, which was dried at 50° C. (<5 mm Hg) to afford 901 mg, and was determined to be the S isomer* (Ex. 267; chiral HPLC: >99.5% ee (no R isomer detected). The isomer that eluted at 10.8-13.0 min was collected as a white solid, which was dried at 50° C. (<5 mm Hg) to afford 865 mg, and was determined to be the R isomer* (Ex. 268; chiral HPLC: 99.2% ee; 0.4% S isomer detected). ¹H NMR and LCMS were consistent with the parent racemate. * The absolute configuration was determined by an independent synthesis of each enantiomer from the corresponding commercially available homochiral alcohols via Mitsunobu reaction. The stereochemical assignments were also consistent by vibrational circular dichroism (VCD) analysis.

References:

US2014/256739,2014,A1 Location in patent:Paragraph 0562