Diethyl cyanophosphonate → N-[4-[(pyrid-2-yl)aminomethyl]phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide

HRID 566131Notes

Reaction equation

HRID 566131 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][C:14]([C:18](O)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)=[CH:25][CH:24]=1.P(C#N)(OCC)(OCC)=O.C(=O)(O)[O-].[Na+]>CN(C=O)C.CN(C1C=CN=CC=1)C.C(N(CC)CC)C>[N:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[NH:30][CH2:29][C:26]1[CH:25]=[CH:24][C:23]([NH:22][C:18]([C:14]2[CH2:15][CH2:16][O:17][C:11]3[CH:10]=[CH:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=4)=[CH:21][C:12]=3[CH:13]=2)=[O:19])=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 76257Diethyl cyanophosphonateHCID 516892Sodium BicarbonateHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acidHCID 11788863N-(4-aminobenzyl)-N-(2-pyridinyl)amine

Product 1

HCID 18472532N-[4-[(pyrid-2-yl)aminomethyl]phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamideYield 21%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 7-(4-methylphenyl)-2,3-dihydrobenzoxepine-4-carboxylic acid (280 mg) and 2-[(4-aminophenyl)methylamino]pyridine (199 mg) in DMF (4 ml) was added, under ice-cooling, diethyl cyanophosphate (0.18 ml) and triethylamine (0.17 ml), and the mixture was stirred at 0° C. for 30 minutes and then at room temperature for 1 hour. To the mixture was added DMAP (1 piece), and the mixture was stirred at room temperature for 18 hours. Under ice-cooling, to the mixture was added sodium bicarbonate solution, and the mixture was extracted with ethyl acetate, washed with brine, dried (anhydrous magnesium sulfate) and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate/hexane=1/1) and recrystallized from ethyl acetate/hexane to give N-[4-[(pyrid-2-yl)aminomethyl]phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 72) (97 mg) as colorless crystals.

Workup

  1. temperaturecooling
  2. temperatureUnder ice-cooling, to the mixture
  3. extractionthe mixture was extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (anhydrous magnesium sulfate)
  6. concentrationconcentrated
  7. customThe residue was purified with silica gel column chromatography (ethyl acetate/hexane=1/1)
  8. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-bd927e1a53c540baa50d9ef56c95559f
Source dataset
uspto-grants-2001_01
Patent number
US06172061B2

Reaction notes

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