Triethylamine → (R)-(1-(2-(6-(3-Hydroxyoxetan-3-yl)pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone

HRID 931222Notes

Reaction equation

HRID 931222 reaction equation
[OH:1][C:2]1([C:6]2[N:11]=[C:10]([CH:12]=O)[CH:9]=[CH:8][CH:7]=2)[CH2:5][O:4][CH2:3]1.Cl.Cl.[NH2:16][C:17]1[CH:18]=[CH:19][C:20]([N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:31])[CH2:25]2)=[N:21][C:22]=1[NH2:23].S(S([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+].C(N(CC)CC)C>C(OCC)(=O)C.O.C(O)C>[OH:1][C:2]1([C:6]2[N:11]=[C:10]([C:12]3[NH:23][C:22]4=[N:21][C:20]([N:24]5[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:32]6[CH2:36][CH2:35][CH2:34][CH2:33]6)=[O:31])[CH2:25]5)=[CH:19][CH:18]=[C:17]4[N:16]=3)[CH:9]=[CH:8][CH:7]=2)[CH2:3][O:4][CH2:5]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 146045Sodium dithionateHCID 898538636-(3-Hydroxyoxetan-3-yl)picolinaldehydeHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride2×

Product 1

HCID 178521008(R)-(1-(2-(6-(3-Hydroxyoxetan-3-yl)pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Into a flask was added 6-(3-hydroxyoxetan-3-yl)picolinaldehyde (54 mg, 0.30 mmol), (R)-(1-(6-amino-5-nitropyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (Intermediate 1, Step 3) (76 mg, 0.24 mmol) and ethanol (1.2 mL). Then sodium dithionate (0.20 g, 1.2 mmol), triethylamine (82 μL, 0.59 mmol) and water (1.0 mL) were added. The solution was heated to 110° C. for 18 h. The mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed with water, washed with a saturated aqueous solution of ammonium chloride, washed with a saturated aqueous solution of sodium bicarbonate and washed with brine. The organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was dried under high vacuum to give a green oil which was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 448.9; HPLC retention time 1.89 min (Method A).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washThe mixture was washed with water
  3. washwashed with a saturated aqueous solution of ammonium chloride
  4. washwashed with a saturated aqueous solution of sodium bicarbonate
  5. washwashed with brine
  6. dry with materialThe organics were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was dried under high vacuum
  10. customto give a green oil which
  11. customwas purified via HPLC

Sources & evidence

ORD record
ord-f881a111a9e14922b9d4cbfd0d41c688
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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