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

HRID 2272715ノート

反応式

HRID 2272715 の反応式
[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

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 12308726Azetidine hydrochlorideHCID 86730074HCID 86730074、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d8b38afdc1b4497db82a956808481712
出典データセット
uspto-grants-2015_09
特許番号
US09120788B2

反応ノート

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