Triethylamine → N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(1-(methylsulfonyl)piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amine

HRID 1522614Notes

Reaction equation

HRID 1522614 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([NH:15][C:16]2[C:17]3[C:18](=[CH:22][N:23]([CH:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[N:24]=3)[N:19]=[CH:20][CH:21]=2)[CH:12]=[CH:11][N:10]=1.C(N(CC)CC)C.[S:38](Cl)([CH3:41])(=[O:40])=[O:39]>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([NH:15][C:16]2[C:17]3[C:18](=[CH:22][N:23]([CH:25]4[CH2:26][CH2:27][N:28]([S:38]([CH3:41])(=[O:40])=[O:39])[CH2:29][CH2:30]4)[N:24]=3)[N:19]=[CH:20][CH:21]=2)[CH:12]=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 54670504N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amine

Product 1

HCID 54670506N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(1-(methylsulfonyl)piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amineYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amine (49 mg, 0.122 mmol) in dichloromethane (3 mL) at 0° C. was added triethylamine (0.051 ml, 0.365 mmol) and mesyl chloride (10.41 μl, 0.134 mmol). The reaction was removed from the ice bath and briefly stirred at room temperature. The reaction mixture was concentrated and subjected to silica column chromatography eluted with 0-5% methanol in dichloromethane using a step gradient (over 24 minutes) to give N-(2-(2-fluoro-5-methylphenyl)pyridin-4-yl)-2-(1-(methylsulfonyl)piperidin-4-yl)-2H-pyrazolo[4,3-b]pyridin-7-amine (12 mg, 21%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.31-2.49 (m, 7H) 2.83-2.95 (m, 3H) 2.95-3.10 (m, 2H) 4.03 (d, J=12.63 Hz, 2H) 4.42-4.66 (m, 1H) 7.03-7.24 (m, 4H) 7.34 (s, 1H) 7.75 (s, 1H) 7.83 (dd, J=7.58, 2.02 Hz, 1H) 8.18 (s, 1H) 8.44 (d, J=4.80 Hz, 1H) 8.65 (d, J=5.56 Hz, 1H). MS [M+H] found 481.4.

Workup

  1. customThe reaction was removed from the ice bath
  2. concentrationThe reaction mixture was concentrated
  3. washeluted with 0-5% methanol in dichloromethane using a step gradient (over 24 minutes)

Sources & evidence

ORD record
ord-be04e736c7d541f9a6ab7bf2761c1e53
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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