Dimethylformamide → 5-[3-Chloro-5-(1-{4-[(2,4-dimethoxybenzyl)amino]-3-methyl-1H-pyrazolo[4,3-c]pyridin-1-yl}ethyl)-6-methoxy-2-methylphenyl]-N,N-dimethylpyridine-2-carboxamide

HRID 1499733Notes

Reaction equation

HRID 1499733 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:4]=1[CH2:5][NH:6][C:7]1C=N[CH:10]=[C:11]2[NH:15][N:14]=[C:13]([CH3:16])[C:12]=12.[H-].[Na+].[Cl:25][C:26]1[C:27]([CH3:48])=[C:28]([C:37]2[CH:38]=[CH:39][C:40]([C:43]([N:45]([CH3:47])[CH3:46])=[O:44])=[N:41][CH:42]=2)[C:29]([O:35][CH3:36])=[C:30]([CH:32](Cl)[CH3:33])[CH:31]=1.[CH3:49][N:50](C)C=O>O>[Cl:25][C:26]1[C:27]([CH3:48])=[C:28]([C:37]2[CH:38]=[CH:39][C:40]([C:43]([N:45]([CH3:47])[CH3:46])=[O:44])=[N:41][CH:42]=2)[C:29]([O:35][CH3:36])=[C:30]([CH:32]([N:15]2[C:11]3[CH:10]=[CH:49][N:50]=[C:7]([NH:6][CH2:5][C:4]4[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[CH:20][C:3]=4[O:2][CH3:1])[C:12]=3[C:13]([CH3:16])=[N:14]2)[CH3:33])[CH:31]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 866776325-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]N,N-dimethylpyridine-2-carboxamideHCID 178490966HCID 178490966, compound

Product 1

HCID 866776655-[3-Chloro-5-(1-{4-[(2,4-dimethoxybenzyl)amino]-3-methyl-1H-pyrazolo[4,3-c]pyridin-1-yl}ethyl)-6-methoxy-2-methylphenyl]-N,N-dimethylpyridine-2-carboxamideYield 49%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

A solution of N-(2,4-dimethoxybenzyl)-3-methyl-1H-pyrazolo[4,3-d]pyridin-4-amine (110 mg, 0.37 mmol) in N,N-dimethylformamide (2 mL) was treated with sodium hydride (30 mg, 0.75 mmol) and stirred at 20° C. for 30 minutes. The reaction mixture was treated with a solution of 5-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]N,N-dimethylpyridine-2-carboxamide (130 mg, 0.34 mmol) in N,N-dimethylformamide (1 mL) and heated at 50° C. overnight. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The combined organic extracts were washed with water and brine, dried with magnesium sulfate, filtered, and concentrated to a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (110 mg, 49%). LCMS for C34H38ClN6O4 (M+H)+: m/z=629.3; Found: 629.1.

Workup

  1. temperatureheated at 50° C. overnight
  2. extractionextracted with ethyl acetate (2×)
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a crude residue
  7. customPurification via preparative LCMS (XBridge C18 column
  8. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-5e7815f5e5cc485d869b4e653bebe1b1
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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