Methyl iodide → HCID 89762052, compound

HRID 528672Notes

Reaction equation

HRID 528672 reaction equation
[CH3:1][O:2][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[C:18](=[O:19])[CH:17]([CH3:20])[O:16][C:15]2[CH:21]=[C:22]([S:25]([N:28](CC3C=CC(OC)=CC=3)[C:29]3[S:30][CH:31]=[CH:32][N:33]=3)(=[O:27])=[O:26])[CH:23]=[CH:24][C:14]1=2.[CH3:43][Si]([N-][Si](C)(C)C)(C)C.[Li+].CI.[Cl-].[NH4+].FC(F)(F)C(O)=O>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:6]=[CH:5][C:4]=1[N:13]1[C:18](=[O:19])[C:17]([CH3:43])([CH3:20])[O:16][C:15]2[CH:21]=[C:22]([S:25]([NH:28][C:29]3[S:30][CH:31]=[CH:32][N:33]=3)(=[O:26])=[O:27])[CH:23]=[CH:24][C:14]1=2

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 89761690HCID 89761690, compound

Product 1

HCID 89762052HCID 89762052, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-(2-Methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2-methyl-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (from the product of Step 2 in Example 263; 110 mg, 0.178 mmol) was dissolved in THF (710 μl) in a 5 mL vial and cooled to 0° C. Lithium bis(trimethylsilyl)amide (1.0 m solution in THF, 69.1 μl, 0.355 mmol) was added dropwise, followed by methyl iodide (16.65 μl, 0.266 mmol), and the reaction was stirred for 30 min at 0° C. until reaction was complete by LCMS. Saturated ammonium chloride solution (aq; 5 mL) was added to the reaction mixture and it was warmed to RT, then extracted with EtOAc (3×5 mL), dried organics over Na2SO4, filtered and concentrated via rotary evaporation. Crude 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2,2-dimethyl-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide was dissolved in DCM (177 μl) then treated with 2,2,2-trifluoroacetic acid (328 μl, 4.42 mmol) and stirred at rt for 30 min until reaction was complete by LCMS. The reaction mixture was concentrated and purified via reverse-phase HPLC with a Waters-Xbridge C18, 19×100 mm, 10 μm column with a gradient 5-95% acetonitrile and water with 0.1% TFA modifier to yield title compound. m/z ESI 514.0 (M+H)+.

Workup

  1. temperaturewas warmed to RT
  2. extractionextracted with EtOAc (3×5 mL), dried organics over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated via rotary evaporation
  5. dissolutionCrude 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2,2-dimethyl-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide was dissolved in DCM (177 μl)
  6. stirringstirred at rt for 30 min until reaction
  7. concentrationThe reaction mixture was concentrated
  8. custompurified via reverse-phase HPLC with a Waters-Xbridge C18, 19×100 mm, 10 μm column with a gradient 5-95% acetonitrile and water with 0.1% TFA modifier

Sources & evidence

ORD record
ord-c756cbbb97d945c2aa77dbea2a60f9b4
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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