Hydrochloric Acid → N-((6-(aminomethyl)-4-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamide

HRID 593816Notes

Reaction equation

HRID 593816 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20]([CH3:36])=[CH:21][C:22]([CH2:27][NH:28]C(=O)OC(C)(C)C)=[N:23][C:24]=2[O:25]C)=[O:16])[C:5]2[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.Cl>O1CCCC1>[NH2:28][CH2:27][C:22]1[NH:23][C:24](=[O:25])[C:19]([CH2:18][NH:17][C:15]([C:4]2[C:5]3[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=3[CH:10]=[C:2]([Br:1])[CH:3]=2)=[O:16])=[C:20]([CH3:36])[CH:21]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68210118tert-butyl((5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate

Product 1

HCID 67467538N-((6-(aminomethyl)-4-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamideYield 82.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of tert-butyl ((5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate (500 mg, 0.894 mmol) in Tetrahydrofuran (THF) (5 mL) was added 6N HCl (15 mL, 15.00 mmol). The reaction was stirred under N2 with heating at 80° C. for 18 hr. The reaction was cooled to RT and evaporated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-40 g, 0 to 10% (5% NH4OH in MeOH) in CH2Cl2). The pure fractions were combined and evaporated to dryness under vacuum. Dissolved with a small volume of CH2Cl2, scratched out by slowly adding hexanes, filtered, washed with hexanes and dried under vacuum to give the product N-((6-(aminomethyl)-4-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamide (328 mg, 0.736 mmol, 82% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.26 (t, J=5.1 Hz, 1H), 7.76 (d, J=1.8 Hz, 1H), 7.33 (d, J=1.0 Hz, 1H), 7.01 (d, J=1.5 Hz, 1H), 6.01 (s, 1H), 5.77 (s, 0H), 4.74 (quin, J=6.6 Hz, 1H), 4.32 (d, J=5.1 Hz, 2H), 3.46 (s, 2H), 2.25 (s, 3H), 2.14 (s, 3H), 1.39 (d, J=6.8 Hz, 6H). MS(ES)+ m/e 445.2 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to RT
  2. customevaporated to dryness under vacuum
  3. customThe remaining was purified by silica gel chromatography (Analogix
  4. customevaporated to dryness under vacuum
  5. dissolutionDissolved with a small volume of CH2Cl2
  6. filtrationfiltered
  7. washwashed with hexanes
  8. customdried under vacuum

Sources & evidence

ORD record
ord-4ab5438cdcb940e8bda9b8c22fe94b56
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

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