Potassium Carbonate → HCID 89761966, compound

HRID 528664Notes

Reaction equation

HRID 528664 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][O:11][C:10]2[CH:14]=[C:15]([S:18]([N:21]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[C:22]3[S:23][CH:24]=[CH:25][N:26]=3)(=[O:20])=[O:19])[CH:16]=[CH:17][C:9]1=2.Br[CH2:37][C:38]#[N:39].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[C:38]([CH2:37][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][O:11][C:10]2[CH:14]=[C:15]([S:18]([N:21]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[C:22]3[S:23][CH:24]=[CH:25][N:26]=3)(=[O:19])=[O:20])[CH:16]=[CH:17][C:9]1=2)#[N:39]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11534BromoacetonitrileHCID 89761693HCID 89761693, compound

Product 1

HCID 89761966HCID 89761966, compoundYield 33.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(2-hydroxyphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (From Example 256, Step 3; 550 mg, 1.080 mmol) and 2-bromoacetonitrile (194 mg, 1.62 mmol) in DMF (10 mL) was added potassium carbonate (447 mg, 3.24 mmol). The reaction mixture was heated at 80° C. for 12 h. After completion, the reaction mixture was cooled to room temperature, diluted with water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with water (3×50 mL), dried over sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 0-30% ethyl acetate in hexane) to yield 4-(2-(cyanomethoxy)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (200 mg, 33.8%). MS (ESI, positive ion) m/z; 549.1 (M+1)

Workup

  1. temperatureAfter completion, the reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. washThe combined organic layer was washed with water (3×50 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude material which
  7. customwas purified by combiflash column chromatography (column size: 12 g; elution: 0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-63cd040bd98b407ab89a191b68de1a0a
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

Loading…