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

HRID 2272715노트

반응식

HRID 2272715 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

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온도
50 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d8b38afdc1b4497db82a956808481712
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09120788B2

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