Dimethylformamide → HCID 86711489, compound

HRID 517549Notes

Reaction equation

HRID 517549 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]([O:9]CC)=O)=[N:4][C:3]=1[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([N:19]2[CH2:24][CH2:23]O[CH2:21][CH2:20]2)[CH:14]=1.[C:25]([O-:28])([O-])=[O:26].[K+].[K+].O/[N:32]=[C:33](\[NH2:45])/[C:34]1[CH:39]=[CH:38][C:37]([O:40][C:41]([F:44])([F:43])[F:42])=[CH:36][CH:35]=1.[CH3:46][N:47](C=O)C>CO>[F:42][C:41]([F:44])([F:43])[C:25]([O-:28])=[O:26].[CH3:46][NH+:47]1[CH2:21][CH2:20][N:19]([C:15]2[CH:16]=[CH:17][CH:18]=[C:13]([CH2:12][C:3]3[N:4]=[C:5]([C:7]4[O:9][N:45]=[C:33]([C:34]5[CH:39]=[CH:38][C:37]([O:40][C:41]([F:44])([F:43])[F:42])=[CH:36][CH:35]=5)[N:32]=4)[O:6][C:2]=3[CH3:1])[CH:14]=2)[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 95803591570043-14-9HCID 86711490HCID 86711490, compound

Product 1

HCID 86711489HCID 86711489, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

To a 25° C. suspension of ethyl 5-methyl-4-(3-morpholinobenzyl)oxazole-2-carboxylate (40 mg, 0.121 mmol) and K2CO3(33.5 mg, 0.242 mmol) in DMF (1211 μl) was added (Z)—N′-hydroxy-4-(trifluoromethoxy)benzimidamide (40.0 mg, 0.182 mmol). The mixture was heated to 150° C. for 12 h. The brown mixture was cooled to RT and partitioned between EtOAc (0.5 mL) and H2O (0.5 mL). The aqueous layer was extracted with EtOAc (3×0.5 mL) and the combined organic layers were washed with H2O (3×0.5 mL) then brine (0.5 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude oil was purified by Biotage (25 g ultra SNAP; 10% EtOAc/Hexane-50% EtOAc) to provide a clear oil. Compounds was loaded onto an Agilent SCX column in MeOH, washed with MeOH until neutral pH, then eluted with 1 N NH3 in MeOH. Evaporation of the volatiles then yielded the desired compound as an orange oil: (8.7 mg, 20%): 1H NMR (600 MHz, CDCl3) δppm 8.24-8.21 (m, 2H), 7.33 (app dd, J=8.8 Hz, 0.7 Hz, 2H), 7.18 (t, J=7.9 Hz, 1H), 6.86 (app t, J=1.8 Hz, 1H), 6.79 (dd, J=8.2 Hz, 2.0 Hz, 1H), 6.73 (d, J=7.9 Hz, 1H), 3.91 (s, 2H), 3.19 (t, J=4.9 Hz, 4H), 2.55 (t, J=4.9 Hz, 4H), 2.37 (s, 3H), 2.33 (s, 3H); MS (ES+) C25H24F3N5O3 requires: 499, found: 500 [M+H]+.

Workup

  1. temperatureThe brown mixture was cooled to RT
  2. custompartitioned between EtOAc (0.5 mL) and H2O (0.5 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (3×0.5 mL)
  4. washthe combined organic layers were washed with H2O (3×0.5 mL)
  5. dry with materialbrine (0.5 mL), dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude oil was purified by Biotage (25 g ultra SNAP; 10% EtOAc/Hexane-50% EtOAc)
  9. customto provide a clear oil
  10. washwashed with MeOH until neutral pH
  11. washeluted with 1 N NH3 in MeOH
  12. customEvaporation of the volatiles

Sources & evidence

ORD record
ord-f367ed10ae264df8a67f2a89078cee4e
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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