Pyridine → HCID 71073340, compound

HRID 2408936Notes

Reaction equation

HRID 2408936 reaction equation
[F:1][CH2:2][CH:3]([OH:5])[CH3:4].N1C=CC=CC=1.[C:12](Cl)(Cl)=[O:13].[NH2:16][CH:17]([CH2:36][C:37]1([F:42])[CH2:41][CH2:40][CH2:39][CH2:38]1)[C:18]([NH:20][C:21]1([CH:25]([OH:35])[C:26](=[O:34])[NH:27][C:28]2[CH:32]=[CH:31][N:30]([CH3:33])[N:29]=2)[CH2:24][CH2:23][CH2:22]1)=[O:19].CCN(C(C)C)C(C)C>C(Cl)Cl>[F:1][CH2:2][CH:3]([O:5][C:12](=[O:13])[NH:16][CH:17]([C:18](=[O:19])[NH:20][C:21]1([CH:25]([OH:35])[C:26](=[O:34])[NH:27][C:28]2[CH:32]=[CH:31][N:30]([CH3:33])[N:29]=2)[CH2:22][CH2:23][CH2:24]1)[CH2:36][C:37]1([F:42])[CH2:38][CH2:39][CH2:40][CH2:41]1)[CH3:4]

Participants

7

Reactant 5

HCID 1049PyridineHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 1016711-Fluoropropan-2-olHCID 71073366HCID 71073366, compound

Product 1

HCID 71073340HCID 71073340, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

1-fluoropropane-2-ol (38 mg, 0.48 mmol) and pyridine (39 μL, 0.48 mmol) were dissolved in DCM (1.5 mL), and the mixture was stirred and cooled to 0° C. Phosgene (1.9 M solution in toluene, 232 μL, 0.44 mmol) was added in one portion and the reaction was allowed to warm to rt and was stirred for 3 h during which a white precipitate formed. In a separate flask, the amine 56-b (36 mg, 0.080 mmol) and DIPEA (45 μL, 0.26 mmol) were dissolved in DCM (1 mL) and the mixture was stirred and cooled to 0° C. 250 μL of the mixture in the first flask were added to the second, and the reaction was monitored by HPLC. Another 250 μL aliquot was added after 15 min and the reaction was stirred for 15 more minutes after which it was quenched by the addition of sat aq NaHCO3 (10 mL) and Et2O (10 mL). The layers were separated and the aqueous phase was extracted with 2×5 mL EtOAc. The combined organic phases were washed with sat aq NaHCO3 (5 mL) and the solvent was removed by rotary evaporation. The product was purified by gradient column chromatography (DCM-10% MeOH in DCM). This gave the title compound as a mixture of diastereomers (22 mg, 57%). ES+ 486.3 [M+H]+.

Workup

  1. temperatureto warm to rt
  2. stirringwas stirred for 3 h during which a white precipitate
  3. customformed
  4. stirringthe mixture was stirred
  5. temperaturecooled to 0° C
  6. additionAnother 250 μL aliquot was added after 15 min
  7. stirringthe reaction was stirred for 15 more minutes after which it
  8. customwas quenched by the addition of sat aq NaHCO3 (10 mL) and Et2O (10 mL)
  9. customThe layers were separated
  10. extractionthe aqueous phase was extracted with 2×5 mL EtOAc
  11. washThe combined organic phases were washed with sat aq NaHCO3 (5 mL)
  12. customthe solvent was removed by rotary evaporation
  13. customThe product was purified by gradient column chromatography (DCM-10% MeOH in DCM)

Sources & evidence

ORD record
ord-5ce63825743641df9a5051529778b0e9
Source dataset
uspto-grants-2014_08
Patent number
US08815809B2

Reaction notes

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