Pyridine → HCID 67441888, compound

HRID 1400807Notes

Reaction equation

HRID 1400807 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:18]4[N:23]=[CH:22][C:21]([CH2:24][N:25]([CH2:33][CH2:34][O:35][CH3:36])[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:20][CH:19]=4)[S:17][C:10]=23)=[CH:4][CH:3]=1.[N:37]1[CH:42]=[CH:41][CH:40]=C[CH:38]=1.ClC(OC1C=CC=CC=1)=[O:45].C1(N)CC1>CN(C=O)C>[CH:42]1([NH:37][C:38](=[O:45])[NH:1][C:2]2[N:7]=[CH:6][C:5]([O:8][C:9]3[CH:14]=[CH:13][N:12]=[C:11]4[CH:15]=[C:16]([C:18]5[N:23]=[CH:22][C:21]([CH2:24][N:25]([CH2:33][CH2:34][O:35][CH3:36])[C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[CH:20][CH:19]=5)[S:17][C:10]=34)=[CH:4][CH:3]=2)[CH2:40][CH2:41]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 67443434HCID 67443434, compound

Product 1

HCID 67441888HCID 67441888, compoundYield 101.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of aniline 27 (634 mg, 1.249 mmol) and pyridine (303 μL, 3.746 mmol) in DMF (15 mL) at 0° C. under nitrogen was added dropwise phenyl chloroformate (415 μL, 3.308 mmol). The reaction mixture was stirred at 0° C. for 2 hrs and cyclopropylamine (433 μL, 6.250 mmol) was slowly added. The reaction mixture was allowed to warm-up to RT over 30 min and was heated at 55° C. for 5 hr then cooled to RT. The reaction mixture was partitioned between AcOEt and a saturated aqueous solution of sodium bicarbonate. The organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate, 1N NaOH, a saturated aqueous solution of ammonium chloride and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by Biotage (SiliaFlash 40 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV). The desired fractions were collected, concentrated and dried under high vacuum to afford the title compound 28 (754 mg, 1.27 mmol, quant. yield) as a pale yellow sticky oil. MS (m/z): 591.6 (M+H).

Workup

  1. temperatureto warm-up to RT over 30 min
  2. temperaturewas heated at 55° C. for 5 hr
  3. temperaturethen cooled to RT
  4. customThe reaction mixture was partitioned between AcOEt
  5. washThe organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate, 1N NaOH
  6. dry with materiala saturated aqueous solution of ammonium chloride and brine, dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by Biotage (SiliaFlash 40 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)
  10. customThe desired fractions were collected
  11. concentrationconcentrated
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-5a2551e2758c4140a814ab63e458217d
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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