2-Fluoropyridine → 3,3-dimethyl-1-(1-(pyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one

HRID 707334노트

반응식

HRID 707334 반응식
Cl.Cl.[CH3:3][C:4]1([CH3:20])[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:5]1=[O:19].C(N(C(C)C)C(C)C)C.F[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1>>[CH3:3][C:4]1([CH3:20])[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH:13]2[CH2:18][CH2:17][N:16]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[CH2:15][CH2:14]2)[C:5]1=[O:19]

참가 물질

4

반응물 3

HCID 97462-FluoropyridineHCID 81531DiisopropylethylamineHCID 866941923,3-dimethyl-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one dihydrochloride2회

생성물 1

HCID 866941913,3-dimethyl-1-(1-(pyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one수율 46.6%

반응 조건

온도
150 °C

실험 절차

A mixture of 3,3-dimethyl-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one dihydrochloride (intermediate 57, 0.1167 g, 0.367 mmol), N-ethyl-N-isopropylpropan-2-amine (0.192 ml, 1.100 mmol), and 2-fluoropyridine (0.189 ml, 2.200 mmol) was stirred at 150° C. for 90 minutes. The mixture was filtered and was purified by reverse phase HPLC (10-55% in 30 min, acetonitrile in water with 0.1% trifluoroacetic acid). The collected fractions were neutralized with solid sodium carbonate and extracted with dichloromethane three times. The organic phase was dried over sodium sulfate and concentrated in vacuo to give 3,3-dimethyl-1-(1-(pyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (0.055 g, 0.171 mmol, 46.5% yield). M+1: 323.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 6 H) 1.72-1.84 (m, 2 H) 2.71-2.85 (m, 2 H) 2.95 (td, J=12.86, 1.86 Hz, 2 H) 4.43-4.65 (m, 3 H) 6.60 (dd, J=6.65, 5.28 Hz, 1 H) 6.71 (d, J=8.61 Hz, 1 H) 6.92 (dd, J=7.24, 5.28 Hz, 1 H) 7.41 (dd, J=7.24, 1.37 Hz, 1 H) 7.47 (ddd, J=8.71, 7.14, 1.96 Hz, 1 H) 8.12 (dd, J=5.18, 1.47 Hz, 1 H) 8.19 (dd, J=4.99, 1.08 Hz, 1 H)

후처리

  1. filtrationThe mixture was filtered
  2. customwas purified by reverse phase HPLC (10-55% in 30 min, acetonitrile in water with 0.1% trifluoroacetic acid)
  3. extractionextracted with dichloromethane three times
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-121f4426d325441498f260660fe158b7
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174992B2

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