Acetic Acid → HCID 118093773, compound

HRID 1056940Notes

Reaction equation

HRID 1056940 reaction equation
[F:1][C:2]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:3]=1[O:4][C:5]1[C:13]2[NH:12][C:11](=[O:14])[N:10]([CH3:15])[C:9]=2[CH:8]=[CH:7][C:6]=1[C:16]1[C:17]2[CH:26]=[CH:25][N:24](S(C3C=CC(C)=CC=3)(=O)=O)[C:18]=2[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1.[H-].[Na+].CI.[OH-].[Na+].O.[C:49](O)(=O)C>CN(C)C=O.C(O)C>[F:1][C:2]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:3]=1[O:4][C:5]1[C:13]2[N:12]([CH3:49])[C:11](=[O:14])[N:10]([CH3:15])[C:9]=2[CH:8]=[CH:7][C:6]=1[C:16]1[C:17]2[CH:26]=[CH:25][NH:24][C:18]=2[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 962WaterHCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 118093812HCID 118093812, compound

Product 1

HCID 118093773HCID 118093773, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(2,4-difluorophenoxy)-1-methyl-5-{6-methyl-1-[(4-methylphenyl)sulfonyl]-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one (30.0 mg, 0.0520 mmol) in N,N-dimethylformamide (0.25 mL) was treated with sodium hydride (4.2 mg, 0.104 mmol) and stirred at RT for 30 min. The reaction mixture was treated with methyl iodide (4.9 μL, 0.0780 mmol) and stirred at RT for 1 h. Analytical LCMS indicated the reaction was complete. The reaction mixture was diluted with ethanol (3.0 mL), treated with 3.0 M sodium hydroxide in water (0.175 mL, 0.525 mmol), and stirred at RT overnight. The reaction was quenched with acetic acid (0.044 mL, 0.780 mmol) and purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min) to give the desired product (14.5 mg, 64%). 1H NMR (400 MHz, DMSO-d6) δ 11.93 (s, 1H), 7.25-7.10 (m, 5H), 6.74-6.62 (m, 1H), 6.56-6.42 (m, 1H), 6.16-6.05 (m, 1H), 3.44 (s, 3H), 3.39 (s, 3H), 3.32 (s, 3H); LCMS calculated for C23H19F2N4O3 (M+H)+: m/z=437.1. found: 437.1.

Workup

  1. stirringstirred at RT for 1 h
  2. stirringstirred at RT overnight
  3. custompurified via preparative LCMS (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-dc81fb3383b841059cbad9126aa0c154
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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