Pyridine → HCID 67442009, compound

HRID 1400852Notes

Reaction equation

HRID 1400852 reaction equation
[NH2:1][C:2]1[CH:35]=[CH:34][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:17]([CH3:33])[C:18]([CH2:21][N:22]([CH2:29][CH2:30][O:31][CH3:32])[C:23]([NH:25][CH:26]5[CH2:28][CH2:27]5)=[O:24])=[CH:19][N:20]=4)[S:15][C:8]=23)=[C:4]([F:36])[CH:3]=1.[N:37]1[CH:42]=C[CH:40]=[CH:39][CH:38]=1.ClC(OC1C=CC=CC=1)=[O:45].C1(N)CC1>CN(C=O)C>[F:36][C:4]1[CH:3]=[C:2]([NH:1][C:42]([NH:37][CH:38]2[CH2:40][CH2:39]2)=[O:45])[CH:35]=[CH:34][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[N:17]([CH3:33])[C:18]([CH2:21][N:22]([CH2:29][CH2:30][O:31][CH3:32])[C:23]([NH:25][CH:26]4[CH2:27][CH2:28]4)=[O:24])=[CH:19][N:20]=3)[S:15][C:8]=12

Participants

6

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 58474674HCID 58474674, compound

Product 1

HCID 67442009HCID 67442009, compoundYield 30.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 160 (283 mg, 0.554 mmol) and pyridine (0.134 mL, 1.663 mmol) in DMF (10 mL) at 0° C. under nitrogen was added phenyl chloroformate (158 mg, 1.386 mmol) and the reaction mixture was stirred at 0° C. for 2 hrs. Cyclopropylamine (0.195 mL, 2.77 mmol) was added and the reaction mixture was heated at 55° C. for 5 hrs. The reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution, then washed a saturated ammonium chloride solution and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by flash column chromatography (eluent EtOAc to 20% MeOH in EtOAc) to afford title compound 161 (100 mg, 30% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.70 (s, 1H), 8.50 (d, J=5.48 Hz, 1H), 7.89 (s, 1H), 7.70 (m, 1H), 7.35 (t, J=9.19 Hz, 1H), 7.19 (m, 1H), 6.93 (s, 1H), 6.64 (d, J=5.48 hz, 1H), 6.56 (s, 1H), 6.51 (m, 1H), 4.54 (s, 2H), 3.82 (s, 3H), 3.27 (m, 2H), 3.25 (m, 2H), 3.19 (s, 3H), 2.54 (m, 2H), 0.63 (m, 2H), 0.55 (m, 2H), 0.41 (m, 2H), 0.37 (m, 2H). MS (m/z)=594.61 (M+H).

Workup

  1. temperaturethe reaction mixture was heated at 55° C. for 5 hrs
  2. customThe reaction mixture was partitioned between EtOAc and saturated sodium bicarbonate solution
  3. washwashed a saturated ammonium chloride solution and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash column chromatography (eluent EtOAc to 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-5bfc601c6edb4c17bff63526b0a68706
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…