Dimethylformamide → HCID 86719524, compound

HRID 1772285Notes

Reaction equation

HRID 1772285 reaction equation
Cl[CH2:2][C:3]1[O:4][C:5]2[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][C:6]=2[N:7]=1.Cl.[N+:17]([C:20]1[CH:25]=[CH:24][C:23]([NH:26][CH:27]2[CH2:32][CH2:31][CH:30]([O:33][CH2:34][C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[O:36])[CH2:29][CH2:28]2)=[CH:22][C:21]=1[C:43]([F:46])([F:45])[F:44])([O-:19])=[O:18].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>CCOC(C)=O>[N+:17]([C:20]1[CH:25]=[CH:24][C:23]([NH:26][CH:27]2[CH2:28][CH2:29][CH:30]([O:33][CH2:34][C:35]([N:37]3[CH2:42][CH2:41][N:40]([CH2:2][C:3]4[O:4][C:5]5[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][C:6]=5[N:7]=4)[CH2:39][CH2:38]3)=[O:36])[CH2:31][CH2:32]2)=[CH:22][C:21]=1[C:43]([F:46])([F:45])[F:44])([O-:19])=[O:18]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 151337512-ChloroMethyl-5-trifluoroMethyl-benzooxazoleHCID 86719503HCID 86719503, compound

Product 1

HCID 86719524HCID 86719524, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloromethyl-5-trifluoromethyl-benzoxazole (50 mg, 0.214 mmol), 2-[4-(4-Nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-1-piperazin-1-yl-ethanone hydrochloride (100 mg, 0.214 mmol), potassium carbonate (60 mg, 0.428 mmol), and DMF (1 mL) was heated at 100° C. for two hours before the reaction mixture was cooled, diluted with EtOAc (60 mL), washed with water (2×40 mL), washed with brine (1×40 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to an orange residue that was purified by silica gel chromatography, eluting with a gradient of 0 to 100% EtOAc in heptanes, to provide 2-[4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-1-[4-(5-trifluoromethyl-benzooxazol-2-ylmethyl)-piperazin-1-yl]-ethanone as a stiff, orange solid (69 mg, 51%). (CI, m/z): [M+H]+ 360; 1H NMR (400 MHz, DMSO-d6): δ 8.17 (s, 1H), 8.05 (d, J=9.23 Hz, 1H), 7.97 (d, J=8.54 Hz, 1H), 7.77 (dd, J=8.57, 1.44 Hz, 1H), 7.43 (d, J=7.71 Hz, 1H), 7.06 (s, 1H), 6.84 (dd, J=9.30, 2.51 Hz, 1H), 3.99 (s, 2H) 4.12 (s, 2H), 3.45 (br s, 5H), 2.52-2.64 (m, 4H), 1.95-2.04 (m, 2H), 1.92 (d, J=10.59 Hz, 2H), 1.28-1.40 (m, 2H), 1.19-1.27 (m, 2H); 19F NMR (376 MHz, DMSO-d6): δ ppm −59.45 (s, 3F)-59.17 (s, 3F).

Workup

  1. temperaturewas cooled
  2. washwashed with water (2×40 mL)
  3. washwashed with brine (1×40 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure to an orange residue that
  7. customwas purified by silica gel chromatography
  8. washeluting with a gradient of 0 to 100% EtOAc in heptanes

Sources & evidence

ORD record
ord-9244e1f13a0a46fbaf36b4e493b8946d
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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