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

HRID 707334Notes

Reaction equation

HRID 707334 reaction equation
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]

Participants

4

Reactant 3

HCID 97462-FluoropyridineHCID 81531DiisopropylethylamineHCID 866941923,3-dimethyl-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one dihydrochloride2×

Product 1

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

Conditions

Temperature
150 °C

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-121f4426d325441498f260660fe158b7
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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