Pyridine → HCID 67441341, compound

HRID 1400880Notes

Reaction equation

HRID 1400880 reaction equation
[NH2:1][C:2]1[CH:36]=[CH:35][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]=[CH:18][N:19]([CH2:21][CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:20]=4)[S:15][C:8]=23)=[C:4]([F:37])[CH:3]=1.[N:38]1[CH:43]=[CH:42][CH:41]=C[CH:39]=1.ClC(OC1C=CC=CC=1)=[O:46].C1(N)CC1>CN(C=O)C.O>[CH:43]1([NH:38][C:39](=[O:46])[NH:1][C:2]2[CH:36]=[CH:35][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[CH:13]=[C:14]([C:16]5[N:17]=[CH:18][N:19]([CH2:21][CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:29])[CH3:27])[CH:20]=5)[S:15][C:8]=34)=[C:4]([F:37])[CH:3]=2)[CH2:41][CH2:42]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 67442973HCID 67442973, compound

Product 1

HCID 67441341HCID 67441341, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of amine 251 (1.2 g, 2.27 mmol) and pyridine (368 μL, 4.55 mmol) in DMF (11 mL) at 0° C. was added phenyl chloroformate (342 μL, 2.73 mmol) and the reaction mixture was stirred for 30 min. Cyclopropylamine (401 μl, 5.69 mmol) was added at 0° C. and the reaction mixture was heated at 60° C. for 45 min. After cooling to RT, the reaction mixture was diluted with water and a saturated solution of ammonium chloride and extracted with AcOEt. The extract was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV), to afford the title compound 252 (1 g, 1.63 mmol, 72% yield) as a beige solid. MS (m/z): 611.70 (M+H).

Workup

  1. temperatureAfter cooling to RT
  2. extractiona saturated solution of ammonium chloride and extracted with AcOEt
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)

Sources & evidence

ORD record
ord-45ac3ebbbd62406ea46a9b7ebe20f6b6
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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