Sodium hydride → HCID 66918801, compound

HRID 2354222Notes

Reaction equation

HRID 2354222 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:26])=[C:11]([NH:13][C:14](=[O:25])[C:15]3[CH:20]=[C:19](F)[CH:18]=[CH:17][C:16]=3[N+:22]([O-:24])=[O:23])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.C(OC([N:34]1[CH2:38][CH2:37][CH2:36][C@@H:35]1[CH2:39][OH:40])=O)(C)(C)C.[H-].[Na+].[Cl-:43].[NH4+]>CN(C=O)C>[ClH:43].[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:26])=[C:11]([NH:13][C:14](=[O:25])[C:15]3[CH:20]=[C:19]([O:40][CH2:39][C@H:35]4[CH2:36][CH2:37][CH2:38][NH:34]4)[CH:18]=[CH:17][C:16]=3[N+:22]([O-:24])=[O:23])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 688279N-(tert-Butoxycarbonyl)-D-prolinolHCID 669189745-fluoro-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-nitrobenzamide

Product 1

HCID 66918801HCID 66918801, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-fluoro-2-nitrobenzamide (3.0 g) and (R)-(+)-1-(tert-butoxycarbonyl)-2-pyrrolidinemethanol (2.54 g) in DMF (45 ml) was added sodium hydride (1.54 g of a 60% dispersion in oil) portion-wise (ice bath cooling). The reaction was stirred for 43 hours at room temperature under an atmosphere of argon. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution (200 ml) and the resulting precipitate was collected by filtration, dissolved in methanol (10 ml) and 4N HCl in dioxane (5 ml) added. The reaction mixture was stirred at room temperature for 16 hours, concentrated and re-precipitated from methanol/ethyl acetate to yield N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-nitro-5-[(2R)-pyrrolidin-2-ylmethoxy]benzamide hydrochloride salt (3.32 g) as a yellow solid; NMR Spectrum: (DMSOd6) 0.64 (m, 2H), 0.75 (m, 2H), 1.83 (m, 1H), 1.95-2.12 (m, 2H), 2.21 (m, 1H), 2.37 s, 3H), 2.91 (m, 1H), 3.30 (m, 2H), 4.02 (m, 1M), 4.45 (m, 1H), 4.55 (m, 1H), 7.37 (m, 3H), 0.70 (d, 1H), 8.02 (s, 1H), 8.29 (d, 1M), 8.49 (d, 1H), 9.50 (s, 1H), 10.22 (s, 1H); Mass Spectrum: M+H+ 439.

Workup

  1. temperatureportion-wise (ice bath cooling)
  2. filtrationthe resulting precipitate was collected by filtration
  3. dissolutiondissolved in methanol (10 ml)
  4. addition4N HCl in dioxane (5 ml) added
  5. stirringThe reaction mixture was stirred at room temperature for 16 hours
  6. concentrationconcentrated
  7. customre-precipitated from methanol/ethyl acetate

Sources & evidence

ORD record
ord-98e610ef6ee64c22a1a5e6e239758d6d
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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