Pyridine → HCID 66717083, compound

HRID 1184443Notes

Reaction equation

HRID 1184443 reaction equation
ClC(Cl)(O[C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.[N:13]1C=CC=C[CH:14]=1.OC[CH2:21][CH2:22][C:23]1[CH:34]=[CH:33][C:26]2[O:27][CH:28]([CH3:32])[C:29](=[O:31])[NH:30][C:25]=2[CH:24]=1.Cl.CN.C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:14][NH:13][C:5](=[O:11])[O:6][CH2:7][CH2:21][CH2:22][C:23]1[CH:34]=[CH:33][C:26]2[O:27][CH:28]([CH3:32])[C:29](=[O:31])[NH:30][C:25]=2[CH:24]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 6364545Methylamine hydrochlorideHCID 67284088HCID 67284088, compound

Product 1

HCID 66717083HCID 66717083, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 20 mL screw cap vial equipped with a magnetic stir bar was added triphosgene (20 mg, 0.068 mmol) in toluene (0.85 mL). The mixture was cooled to 0° C. and pyridine (0.017 mL, 0.21 mmol) was added followed by 188 (38 mg, 0.17 mmol) in toluene (0.5 mL). The reaction was stirred at 0° C. for 1 h then room temperature overnight. The reaction was concentrated in vacuo then taken up in DCM (1.0 mL) and cooled to 0° C. Methylamine HCl (57 mg, 0.85 mmol) was added followed by triethylamine (0.237 mL, 1.7 mmol). The reaction was allowed to warm to room temperature and was stirred for 18 h. The reaction was concentrated in vacuo and the residue was purified by preparative HPLC-MS using 20-45% MeCN in water as the gradient. The appropriate fractions were collected and concentrated in vacuo to give the title compound as a white solid (14 mg, 29% yield): 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40 (d, J=6.82 Hz, 3H) 1.72-1.83 (m, 2H) 2.51-2.55 (m, 2 H) 2.56 (d, J=4.80 Hz, 3H) 3.92 (t, J=6.57 Hz, 2H) 4.57-4.64 (m, 1H) 6.69 (d, J=1.77 Hz, 1 H) 6.74 (dd, J=8.08, 2.02 Hz, 1H) 6.86 (d, J=8.08 Hz, 1H) 6.94-7.03 (m, 1H) 10.60 (s, 1H). ESI-MS: m/z 279.2 (M+H)+.

Workup

  1. customTo a 20 mL screw cap vial
  2. customequipped with a magnetic stir bar
  3. customroom temperature overnight
  4. concentrationThe reaction was concentrated in vacuo
  5. temperaturecooled to 0° C
  6. temperatureto warm to room temperature
  7. stirringwas stirred for 18 h
  8. concentrationThe reaction was concentrated in vacuo
  9. customthe residue was purified by preparative HPLC-MS
  10. customThe appropriate fractions were collected
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-997bd76599b648c4bca36a4c2bb0877f
Source dataset
uspto-grants-2014_03
Patent number
US08669249B2

Reaction notes

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