Diisopropylethylamine → HCID 67236264, compound

HRID 1023591Notes

Reaction equation

HRID 1023591 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[NH2:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[C:32]([C:38]([CH3:40])=[CH2:39])[CH:31]=2)=[N:27][CH:28]=1.[Cl-].[CH3:42][C@@:43]([NH3+:50])([CH2:48][CH3:49])[C:44](OC)=[O:45]>C(Cl)Cl>[CH2:48]([C@:43]1([CH3:42])[C:44](=[O:45])[N:22]([C:23]2[CH:24]=[CH:25][C:26]([O:29][C:30]3[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[C:32]([C:38]([CH3:40])=[CH2:39])[CH:31]=3)=[N:27][CH:28]=2)[C:5](=[O:11])[NH:50]1)[CH3:49]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 67235042HCID 67235042, compound2×HCID 178449862HCID 178449862, compound

Product 1

HCID 67236264HCID 67236264, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of triphosgene (118 mg, 0.40 mmol) in dry DCM (3 mL) at 0° C. DIPEA (0.695 ml, 4.0 mmol) was added followed by a solution of 4-[(5-amino-2-pyridinyl)oxy]-2-(1-methylethenyl)benzonitrile (Intermediate 154, 100 mg) in dry DCM (6 mL) slowly added (5 minutes). After that (2R)-2-methyl-1-(methyloxy)-1-oxo-2-butanaminium chloride (268 mg, 1.6 mmol) dissolved in dry DCM (3 mL) was added at the same temperature and the reaction mixture was stirred for 45 minutes at 0° C. The reaction was quenched with water and aqueous buffer (pH 3) was added while the pH was allowed to reach ˜5-6. Ethyl acetate (40 ml) was added and two phases were separated. The organic layer was washed with brine (2×10 ml), dried (Na2SO4), filtered and evaporated affording the urea intermediate as yellow foam. This urea was dissolved in MeOH (10 mL), NaOMe (10 mg) was added and the reaction mixture was refluxed for 45 minutes under stirring. After cooling the mixture was quenched with an aqueous saturated solution of ammonium chloride (10 mL) and diluted with ethyl acetate (20 mL). Two phases were separated and the organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography on silica gel (SNAP 10 g) eluting from 75:25 to 50:50 cyclohexane/ethyl acetate affording the title compound as a white solid (100 mg).

Workup

  1. customat 0° C
  2. additionslowly added (5 minutes)
  3. additionwas added at the same temperature
  4. customThe reaction was quenched with water and aqueous buffer (pH 3)
  5. additionwas added while the pH
  6. additionEthyl acetate (40 ml) was added
  7. customtwo phases were separated
  8. washThe organic layer was washed with brine (2×10 ml)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-79bb66893207457b9386b98be3219952
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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