Methylamine → 3-((7-(4-chlorophenyl)-3-oxo-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)methyl)-N-methyl-6-(trifluoromethyl)picolinamide

HRID 2101347노트

반응식

HRID 2101347 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:31])[N:15]([CH2:17][C:18]4[C:19]([C:28](Cl)=[O:29])=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:32]2[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=2)=[CH:4][CH:3]=1.CN.C[CH2:41][N:42](CC)CC>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:31])[N:15]([CH2:17][C:18]4[C:19]([C:28]([NH:42][CH3:41])=[O:29])=[N:20][C:21]([C:24]([F:26])([F:25])[F:27])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:32]2[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=2)=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 6329MethylamineHCID 8471TriethylamineHCID 57799456HCID 57799456, 화합물

생성물 1

HCID 577994133-((7-(4-chlorophenyl)-3-oxo-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)methyl)-N-methyl-6-(trifluoromethyl)picolinamide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

To a stirring solution of 3-((7-(4-chlorophenyl)-3-oxo-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)methyl)-6-(trifluoromethyl)picolinoyl chloride (36 mg, 0.066 mmol) in anhydrous THF (1 mL) at 0° C. was added 2 M methylamine solution in THF (0.33 mL, 0.66 mmol), followed by Et3N (0.046 mL, 0.33 mmol). The resulting mixture was stirred at 0° C. for 30 min, then at room temperature for 16 h. Analysis by HPLC/MS indicated the starting acid chloride had been consumed and the desired product had formed. The reaction mixture was diluted with water and extracted with EtOAc (15 mL×2). The combined EtOAc extracts were washed with saturated aqueous NaCl, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified using preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 50% to 100% B over 8 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 12 mg (34%) of the title compound as a pale yellow powder. HPLC/MS: retention time=2.83 min, [M+H]+=539.2.

후처리

  1. waitat room temperature for 16 h
  2. customhad been consumed

출처 및 근거

ORD 기록
ord-17b275456a1f40968e7492a344fdee7b
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572808B2

반응 노트

불러오는 중…