Triethylamine → 1-(2,2-Dimethylpropyl)-3-methyl-5-{(1R,25)-2-[2-(methylsulfonyl)ethyl]-cyclopropyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629912Notes

Reaction equation

HRID 629912 reaction equation
[CH3:1][C:2]([CH3:22])([CH3:21])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C@@H:13]3[CH2:15][C@H:14]3[CH2:16][CH2:17]O)=[CH:10][CH:11]=2)[N:6]([CH3:19])[C:5]1=[O:20].C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>C(Cl)Cl>[CH3:1][C:2]([CH3:22])([CH3:21])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C@@H:13]3[CH2:15][C@H:14]3[CH2:16][CH2:17][S:31]([CH3:30])(=[O:33])=[O:32])=[CH:10][CH:11]=2)[N:6]([CH3:19])[C:5]1=[O:20]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 1177023211-(2,2-Dimethylpropyl)-5-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 1177023681-(2,2-Dimethylpropyl)-3-methyl-5-{(1R,25)-2-[2-(methylsulfonyl)ethyl]-cyclopropyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

1-(2,2-Dimethylpropyl)-5-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (32-4, 46.4 mg, 0.15 mmol, 1.0 equiv) was added to anhydrous DCM (1.5 mL) and cooled to −10° C. Triethylamine (90 μL, 0.64 mmol, 4.2 equiv) and methanesulfonyl chloride (26 μL, 0.33 mmol, 2.2 equiv) were added sequentially and the resulting reaction mixture was stirred for 1 min. Following this duration, TLC showed complete consumption of 32-4. The reaction mixture was partitioned between ethyl acetate (5 mL) and saturated NaHCO3 (5 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×5 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give 32-5 as a clear, yellow oil. The crude product was carried forward without further purification.

Workup

  1. customthe resulting reaction mixture
  2. customconsumption of 32-4
  3. customThe reaction mixture was partitioned between ethyl acetate (5 mL) and saturated NaHCO3 (5 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×5 mL)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give 32-5 as a clear, yellow oil
  10. customThe crude product was carried forward without further purification

Sources & evidence

ORD record
ord-3aa738fae5da4d5e8ddb4b2e199d340d
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

Loading…