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

HRID 873386Notes

Reaction equation

HRID 873386 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20]([O:28]C)=[N:21][C:22]([CH2:26][OH:27])=[CH:23][C:24]=2[CH3:25])=[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>[Br:1][C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:28])[NH:21][C:22]([CH2:26][OH:27])=[CH:23][C:24]=2[CH3:25])=[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

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 674661066-bromo-N-((6-(hydroxymethyl)-2-methoxy-4-methylpyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide

Product 1

HCID 546711986-bromo-N-((6-(hydroxymethyl)-4-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamideYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 6-bromo-N-((6-(hydroxymethyl)-2-methoxy-4-methylpyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (500 mg, 1.086 mmol) in tetrahydrofuran (5 mL) was added 6 N 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, SF25-60 g, 4% MeOH in CH2Cl2). The pure fractions were combined and evaporated to dryness under vacuum. Triturated with a small volume of water, filtered, washed with water and dried under vacuum to give the product 6-bromo-N-((6-(hydroxymethyl)-4-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (189 mg, 0.423 mmol, 39.0% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=11.30 (s, 1 H), 8.27 (t, J=4.9 Hz, 1 H), 7.76 (d, J=1.8 Hz, 1 H), 7.33 (s, 1 H), 7.01 (d, J=1.8 Hz, 1 H), 6.05 (s, 1 H), 5.38 (t, J=5.9 Hz, 1 H), 4.74 (dt, J=6.7, 13.2 Hz, 1 H), 4.32 (d, J=5.1 Hz, 2 H), 4.25 (d, J=5.8 Hz, 2 H), 2.26 (s, 3 H), 2.13 (s, 3 H), 1.39 (d, J=6.6 Hz, 6 H). MS(ES)+m/e 446.1 [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. customTriturated with a small volume of water
  6. filtrationfiltered
  7. washwashed with water
  8. customdried under vacuum

Sources & evidence

ORD record
ord-c6ca8b8dd2434e5497a9d0bdafc1568d
Source dataset
uspto-grants-2015_03
Patent number
US08975291B2

Reaction notes

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