Pyridine → HCID 86658600, compound

HRID 1400930Notes

Reaction equation

HRID 1400930 reaction equation
[C:1]([C:3]1[S:11][C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[O:12][C:13]2[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][C:14]=2[F:20])[CH:4]=1)#[CH:2].[N:21]1[CH:26]=[CH:25][CH:24]=C[CH:22]=1.ClC(OC1C=CC=CC=1)=[O:29].C1(N)CC1>C1COCC1.CCOC(C)=O.CCOCC.CN(C=O)C>[CH:26]1([NH:21][C:22]([NH:17][C:16]2[CH:18]=[CH:19][C:13]([O:12][C:9]3[CH:8]=[CH:7][N:6]=[C:5]4[CH:4]=[C:3]([C:1]#[CH:2])[S:11][C:10]=34)=[C:14]([F:20])[CH:15]=2)=[O:29])[CH2:24][CH2:25]1

Participants

9

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 59457668HCID 59457668, compound

Product 1

HCID 86658600HCID 86658600, compoundYield 76%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 370 (102 mg, 0.359 mmol) and pyridine (0.058 mL, 2 eq, 0.718 mmol) in THF (5 ml)/DMF (2 ml) at 0° C. under nitrogen was added phenyl chloroformate (0.068 mL, 1.5 eq, 0.538 mmol) and the reaction mixture was stirred at 0° C. for 1 hr. Cyclopropylamine (102 mg, 5 eq, 1.794 mmol) was added and the reaction mixture was heated at 55° C. for 3 hrs. The mixture was then cooled to RT, diluted with EtOAc then washed sequentially with saturated solutions of NH4Cl, NaHCO3 and brine. The organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified via column chromatography (eluent EtOAc to 40% MeOH in EtOAc) to afford the title compound 371 (100 mg, 76% yield) as an off-white powder after trituration with Et2O. MS (m/z): 368.23 (M+H)

Workup

  1. temperaturethe reaction mixture was heated at 55° C. for 3 hrs
  2. temperatureThe mixture was then cooled to RT
  3. washthen washed sequentially with saturated solutions of NH4Cl, NaHCO3 and brine
  4. dry with materialThe organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via column chromatography (eluent EtOAc to 40% MeOH in EtOAc)

Sources & evidence

ORD record
ord-b06d357843504d58af500a3578d3fb1b
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…