Pyridine → HCID 67440529, compound

HRID 1400850Notes

Reaction equation

HRID 1400850 reaction equation
[NH2:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:17]=[N:18][N:19]([CH2:21][CH2:22][OH:23])[CH:20]=4)[S:15][C:8]=23)=[C:4]([F:26])[CH:3]=1.[N:27]1[CH:32]=C[CH:30]=[CH:29][CH:28]=1.Cl[C:34](OC1C=CC=CC=1)=[O:35].[CH:43]1([NH2:46])[CH2:45][CH2:44]1.CN(C=[O:51])C>>[CH:43]1([NH:46][C:34](=[O:35])[O:23][CH2:22][CH2:21][N:19]2[CH:20]=[C:16]([C:14]3[S:15][C:8]4[C:9](=[N:10][CH:11]=[CH:12][C:7]=4[O:6][C:5]4[CH:24]=[CH:25][C:2]([NH:1][C:32]([NH:27][CH:28]5[CH2:29][CH2:30]5)=[O:51])=[CH:3][C:4]=4[F:26])[CH:13]=3)[CH:17]=[N:18]2)[CH2:45][CH2:44]1

Participants

6

Reactant 5

HCID 1049PyridineHCID 6228DimethylformamideHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 58474793HCID 58474793, compound

Product 1

HCID 67440529HCID 67440529, compoundYield 23%

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 156 (900 mg, 2.430 mmol) and pyridine (0.59 mL, 7.29 mmol) in DMF (10 mL) at 0° C. under nitrogen was added phenyl chloroformate (951 mg, 6.07 mmol) and the reaction mixture was stirred at 0° C. for 2 hrs. Cyclopropylamine (694 mg, 12.15 mmol) was added and the reaction mixture was heated at 55° C. for 5 hrs. The reaction mixture was then partitioned between EtOAc and saturated sodium bicarbonate solution. The organic phase was collected then washed a saturated ammonium chloride solution and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (eluent EtOAc to 30% MeOH in EtOAc) to afford title compound 157 (300 mg, 23% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.69 (s, 1H), 8.43 (d, J=5.47 Hz, 1H), 8.33 (s, 1H), 8.03 (s, 1H), 7.72 (m, 1H), 7.70 (m, 1H), 7.41 (m, 1H), 7.35 (t, J=9.19 Hz, 1H), 7.19 (m, 1H), 6.54 (m, 2H), 4.34 (m, 4H), 2.53 (m, 1H), 2.49 (m, 1H), 0.65 (m, 2H), 0.54 (m, 2H), 0.43 (m, 2H), 0.36 (m, 2H). MS (m/z)=537.58 (M+H).

Workup

  1. temperaturethe reaction mixture was heated at 55° C. for 5 hrs
  2. customThe reaction mixture was then partitioned between EtOAc and saturated sodium bicarbonate solution
  3. customThe organic phase was collected
  4. washthen washed a saturated ammonium chloride solution and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (eluent EtOAc to 30% MeOH in EtOAc)

Sources & evidence

ORD record
ord-d28295e844b14b43996c12d8b6c838af
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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