4-(Morpholin-4-yl)benzoic acid → HCID 9835852, compound

HRID 888006Notes

Reaction equation

HRID 888006 reaction equation
C(O[C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH2:15])=[O:7])(C)(C)C.[O:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:30]=[CH:29][C:25](C(O)=O)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1>CN(C=O)C>[NH2:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[NH:8][C:6](=[O:7])[C:25]1[CH:24]=[CH:23][C:22]([N:19]2[CH2:18][CH2:17][O:16][CH2:21][CH2:20]2)=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 3452784-(Morpholin-4-yl)benzoic acidHCID 676311N-(tert-Butoxycarbonyl)-1,2-phenylenediamine

Product 1

HCID 9835852HCID 9835852, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(N-t-butoxycarbonylamino)-2-aminobenzene (Method 17; 104 mg, 0.5 mmol) in DMF (1.6 ml) was added to 4-morpholinobenzoic acid (149 mg, 0.5 mmol) followed by 4-(4,6-dimethoxy-1,3,5-triazinyl-2-yl)-4-methylmorpholinium chloride (Method 18, 138 mg, 0.5 mmol) and the reaction mixture stirred at ambient temperature for 48 hours. The solvent was removed in vacuo and the resultant residue partitioned between ethyl acetate and water. The organic phase was separated, then washed with water, brine and dried over sodium sulfate then filtered. The organic extracts were concentrated by half and a 4M solution of hydrogen chloride in 1,4-dioxane (1 ml) added. The reaction mixture was stirred at ambient temperature for a further 64 hours and the resultant precipitate was collected by filtration. This solid was purified by preparative mass triggered HPLC, eluting with an increasing gradient of acetonitrile in water (which contains 5% (v/v) of a 1% (v/v) solution of formic acid in methanol) to afford the title compound (17 mg, 12%); NMR Spectrum: (DMSO-d6) 3.25 (m, 4H), 3.76 (m, 4H), 4.83 (s, 2H), 6.60 (m, 1H), 6.79 (dd, 1H), 6.96 (m, 1H), 7.01 (d, 2H), 7.16 (dd, 1H), 7.90 (d, 2H), 9.31 (brs, 1H); Mass Spectrum: M+H+ 298.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe resultant residue partitioned between ethyl acetate and water
  3. customThe organic phase was separated
  4. washwashed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationthen filtered
  7. concentrationThe organic extracts were concentrated by half
  8. additiona 4M solution of hydrogen chloride in 1,4-dioxane (1 ml) added
  9. stirringThe reaction mixture was stirred at ambient temperature for a further 64 hours
  10. filtrationthe resultant precipitate was collected by filtration
  11. customThis solid was purified by preparative mass
  12. washeluting with an increasing gradient of acetonitrile in water (which

Sources & evidence

ORD record
ord-bcff7ec5dd464c898c15d5417f2a7330
Source dataset
uspto-grants-2012_08
Patent number
US08247562B2

Reaction notes

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