Triethylamine → N-[6-(Methylamino)pyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

HRID 1516384Notes

Reaction equation

HRID 1516384 reaction equation
C(P(=O)(OCC)OCC)#N.[F:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=1)[C:16]([C:29](O)=[O:30])=[CH:15]2.[NH2:32][C:33]1[CH:34]=[N:35][C:36]([NH:39][CH3:40])=[CH:37][CH:38]=1.C(N(CC)CC)C>CN(C)C=O>[CH3:40][NH:39][C:36]1[N:35]=[CH:34][C:33]([NH:32][C:29]([C:16]2[N:17]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)[C:18]3[C:14]([CH:15]=2)=[CH:13][C:12]([F:11])=[CH:20][CH:19]=3)=[O:30])=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 119790N2-Methylpyridine-2,5-diamineHCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid

Product 1

HCID 23725112N-[6-(Methylamino)pyridin-3-yl]-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamideYield 86.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.27 ml (1.67 mmol) of diethyl cyanophosphonate is added dropwise at 20° C. under argon to a solution of 0.4 g (1.39 mmol) of 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid (obtained in step 1.1) and 0.216 g (1.67 mmol) of 3-amino-6-(methylamino)pyridine (WO2005/028452) in 10 ml of dry dimethylformamide. The mixture is stirred for 10 minutes and then 0.43 ml (3.08 mmol) of triethylamine is added dropwise. The mixture is stirred at ambient temperature for 18 hours and concentrated under reduced pressure, and then the residue is taken up in 50 ml of ethyl acetate. This solution is then successively washed with three times 20 ml of a saturated sodium hydrogencarbonate solution, 50 ml of water and 20 ml of a saturated sodium chloride solution and then dried over sodium sulfate, filtered and concentrated under reduced pressure. The solid obtained is triturated from hot isopropyl ether. 0.471 g of a solid is obtained, which solid is dried under reduced pressure.

Workup

  1. stirringThe mixture is stirred at ambient temperature for 18 hours
  2. concentrationconcentrated under reduced pressure
  3. washThis solution is then successively washed with three times 20 ml of a saturated sodium hydrogencarbonate solution, 50 ml of water and 20 ml of a saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe solid obtained
  8. customis triturated from hot isopropyl ether

Sources & evidence

ORD record
ord-8f6b5e4af277419c97586ddc439f99ea
Source dataset
uspto-grants-2012_07
Patent number
US08227489B2

Reaction notes

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