Potassium Carbonate → Azetidin-1-yl-[3-(4-chloro-3-fluorophenyl)imidazo[4,5-b]pyridin-2-yl]methanone

HRID 2272715Notes

Reaction equation

HRID 2272715 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]=[C:9]2[C:17](Cl)(Cl)Cl)=[CH:4][C:3]=1[F:21].Cl.[NH:23]1[CH2:26][CH2:25][CH2:24]1.C(=O)([O-])[O-:28].[K+].[K+]>C(#N)C.O>[N:23]1([C:17]([C:9]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([F:21])[CH:4]=3)[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]=2)=[O:28])[CH2:26][CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 12308726Azetidine hydrochlorideHCID 86730074HCID 86730074, compound

Product 1

HCID 78322601Azetidin-1-yl-[3-(4-chloro-3-fluorophenyl)imidazo[4,5-b]pyridin-2-yl]methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

3-(4-Chloro-3-fluorophenyl)-2-(trichloromethyl)-3H-imidazo[4,5-b]pyridine (C20) (50 mg, 0.14 mmol) was dissolved in a 3:1 mixture of acetonitrile and water (1.4 mL). Azetidine hydrochloride (25.6 mg, 0.274 mmol) was added, followed by an aqueous solution of potassium carbonate (4 M, 0.15 mL, 0.60 mmol), and the reaction mixture was heated at 50° C. for 22 hours, then at 80° C. for 3 hours, and finally at 100° C. for 18 hours. The layers were separated, and the organic layer was concentrated in vacuo; purification via reversed phase HPLC (Column: Waters Sunfire C18, 5 μm; Mobile phase A: 0.05% trifluoroacetic acid in water (v/v); Mobile phase B: 0.05% trifluoroacetic acid in acetonitrile (v/v); Gradient: 30% to 50% B) afforded the product. Yield: 17 mg, 51 μmol, 36%. LCMS m/z 331.1, 333.1 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 8.45 (dd, J=4.6, 1.5 Hz, 1H), 8.30 (dd, J=7.9, 1.3 Hz, 1H), 7.76 (dd, J=8.3, 8.3 Hz, 1H), 7.73 (dd, J=10.1, 2.2 Hz, 1H), 7.46 (dd, J=8.1, 4.6 Hz, 1H), 7.40-7.43 (m, 1H), 4.64-4.68 (m, 2H), 4.02-4.07 (m, 2H), 2.29-2.35 (m, 2H).

Workup

  1. waitfinally at 100° C. for 18 hours
  2. customThe layers were separated
  3. concentrationthe organic layer was concentrated in vacuo
  4. custompurification via reversed phase HPLC (Column: Waters Sunfire C18, 5 μm; Mobile phase A: 0.05% trifluoroacetic acid in water (v/v); Mobile phase B: 0.05% trifluoroacetic acid in acetonitrile (v/v); Gradient: 30% to 50% B)
  5. customafforded the product

Sources & evidence

ORD record
ord-d8b38afdc1b4497db82a956808481712
Source dataset
uspto-grants-2015_09
Patent number
US09120788B2

Reaction notes

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