Hydrochloric Acid → HCID 178436714, compound

HRID 515848Notes

Reaction equation

HRID 515848 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:24](N(OC)C)=[O:25])[C:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:6](/[N:10]=[N:11]/[N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:7]=1[C:8]#[CH:9].[CH3:30][Mg]Cl.Cl>O1CCCC1.O>[Cl:1][C:2]1[C:7]([C:8]#[CH:9])=[C:6](/[N:10]=[N:11]/[N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:4]([C:24](=[O:25])[CH3:30])[CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 178418332HCID 178418332, compound2×HCID 178436722HCID 178436722, compound

Product 1

HCID 178436714HCID 178436714, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
20 °C

Procedure

A solution of 4-chloro-6-[(1E)-3 ,3 -diethyltriaz-1-en-1-yl]-5-ethynyl-3′-fluoro-N-methoxy-N-methylbiphenyl-2-carboxamide (2.7 g, 6.6 mmol) in tetrahydrofuran (26 mL) at 0° C. was treated with 3 M of methylmagnesium chloride in tetrahydrofuran (6.6 mL, 20 mmol) dropwise and stirred at 20° C. for 1 hour. The reaction mixture still contained some starting material and was, therefore, cooled to 0° C., treated with additional 3 M of methylmagnesium chloride in tetrahydrofuran (2.2 mL, 6.6 mmol) dropwise, and stirred at 20° C. for 2 hours. The reaction mixture was cooled to 0° C., quenched with 1 M hydrogen chloride in water (26 mL, 26 mmol), poured into 0.1 M hydrogen chloride in water (100 mL) and extracted with ethyl acetate (150 mL). The organic layer was separated, washed with saturated sodium bicarbonate and brine, dried with sodium sulfate, filtered, and concentrated to give a crude oil. Purification by flash column chromatography using ethyl acetate in hexanes (0% - 20%) gave the desired product (2.3 g, 93%). LCMS for C20H20ClFN3O (M+H)+: m/z=372.1; Found: 371.9.

Workup

  1. temperaturecooled to 0° C.
  2. stirringstirred at 20° C. for 2 hours
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. extractionextracted with ethyl acetate (150 mL)
  5. customThe organic layer was separated
  6. washwashed with saturated sodium bicarbonate and brine
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a crude oil
  11. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-b583ef406d3f4f61a01348dd98cb5d8a
Source dataset
uspto-grants-2015_08
Patent number
US09108984B2

Reaction notes

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