2-Aminooxazole → 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(oxazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528564Notes

Reaction equation

HRID 528564 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[N:13]1[CH2:18][CH2:17][O:16][C:15]2[CH:19]=[C:20]([S:23](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:25])=[O:24])[CH:21]=[CH:22][C:14]1=2)#[N:2].[O:38]1[CH:42]=[CH:41][N:40]=[C:39]1[NH2:43].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C(O)(=O)C.C1COCC1>[C:1]([C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:6]=[CH:5][C:4]=1[N:13]1[CH2:18][CH2:17][O:16][C:15]2[CH:19]=[C:20]([S:23]([NH:43][C:39]3[O:38][CH:42]=[CH:41][N:40]=3)(=[O:25])=[O:24])[CH:21]=[CH:22][C:14]1=2)#[N:2]

Participants

6

Reactant 3

HCID 5585212-Aminooxazole2×HCID 2733832Lithium Hexamethyldisilazide2×HCID 89762001perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate

Product 1

HCID 717117654-(2-cyano-4-(trifluoromethyl)phenyl)-N-(oxazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A round bottom flask was charged with perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (INTERMEDIATE AB, 40.69 mg, 0.074 mmol), oxazole-2-amine (9.32 mg, 0.11 mmol, Ryan Scientific, Mt. Pleasant, S.C.) and THF (1 mL) to give a clear, colorless solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (155 μl, 0.155 mmol) was added dropwise over 30 s to give a light-yellow solution. After 5 min, the flask was lowered into an ice bath for 1 h. Additional portions of oxazole-2-amine (ca. 5 mg) and LHMDS solution (0.05 mL) were added in sequence. After an additional 45 min, glacial acetic acid (1 drop) was added. The mixture was concentrated under a vacuum. The product was purified by chromatography on silica gel (12 g column with 0 to 10% MeOH/DCM) to give 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(oxazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.86 (br. s., 1 H), 8.38 (d, J=2.1 Hz, 1 H), 8.05 (dd, J=1.8, 8.8 Hz, 1 H), 7.71 (d, J=8.6 Hz, 1 H), 7.59 (d, J=1.7 Hz, 1 H), 7.31 (d, J=2.1 Hz, 1 H), 7.26-7.17 (m, 2 H), 6.80 (d, J=8.5 Hz, 1 H), 4.36-4.27 (m, 2 H), 3.87-3.82 (m, 2 H). m/z (ESI) 451.4 (M+H)+.

Workup

  1. customto give a clear, colorless solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customto give a light-yellow solution
  4. waitthe flask was lowered into an ice bath for 1 h
  5. waitAfter an additional 45 min
  6. concentrationThe mixture was concentrated under a vacuum
  7. customThe product was purified by chromatography on silica gel (12 g column with 0 to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-cd6705a1dcee4378b380267bb9267cdd
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

Loading…