(R)-1,2-Epoxypropane → HCID 178488909, compound

HRID 591940Notes

Reaction equation

HRID 591940 reaction equation
[Cl:1][C:2]1[C:3]([NH:25][C@@H:26]2[C@@H:31]3[CH2:32][C@@H:28]([CH:29]=[CH:30]3)[C@@H:27]2[C:33]([NH2:35])=[O:34])=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=3[CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[NH:8][C:5]2=[N:6][CH:7]=1.[CH2:36]1[O:39][C@@H:37]1[CH3:38]>CO>[Cl:1][C:2]1[C:3]([NH:25][C@@H:26]2[C@@H:31]3[CH2:32][C@@H:28]([CH:29]=[CH:30]3)[C@@H:27]2[C:33]([NH2:35])=[O:34])=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=3[CH:19]3[CH2:20][CH2:21][N:22]([CH2:36][C@@H:37]([OH:39])[CH3:38])[CH2:23][CH2:24]3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 146261(R)-1,2-EpoxypropaneHCID 178488908HCID 178488908, compound2×

Product 1

HCID 178488909HCID 178488909, compoundYield 16.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(1S,2S,3R,4R)-3-[6-Chloro-2-(4-methoxy-2-piperidin-4-yl-phenyl)-3H-imidazo[4,5-b]pyridine-7-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (Compound XXX) (60 mg, 0.1 mmol) was stirred with (R)-propylene oxide (8.0 mg, 1.0 mmol) in methanol (5 mL) in a sealed tube overnight. The reaction was concentrated and the product purified by reverse phase chromatography (Gilson). Desired fractions were collected, combined, and neutralized by partitioning between dichloromethane and saturated sodium bicarbonate solution. The organic layer was separated, dried (magnesium sulfate) and concentrated to afford the title compound as a white solid 9 mg, 10%). 1H NMR (d-chloroform): 13.83 (br s, 1H), 7.89 (s, 1H), 7.66 (d, J=8 Hz, 1H), 7.07 (s, 1H), 6.97 (d, J=8 Hz, 1H), 6.32-6.28 (m, 3H), 5.62 (m, 1H), 5.22 (m, 2H), 3.95 (s, 3H), 3.87 (m, 1H), 3.70 (m, 1H), 3.15 (s, 1H), 3.07 (m, 1H), 2.93 (m, 2H), 2.74 (d, J=7 Hz, 1H), 2.36 (m, 4H), 1.99 (m, 3H), 1.76 (m, 3H), 1.28 (s, 1H), 1.18 (d, J=5 Hz, 3H). MS: 551.18 (M+H). HPLC retention time: 1.99 minutes (G Method).

Workup

  1. concentrationThe reaction was concentrated
  2. customthe product purified by reverse phase chromatography (Gilson)
  3. customDesired fractions were collected
  4. customby partitioning between dichloromethane and saturated sodium bicarbonate solution
  5. customThe organic layer was separated
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d6d3a6d01cda40118b237514a5c1af9d
Source dataset
uspto-grants-2016_01
Patent number
US09238656B2

Reaction notes

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