Triethyl phosphite → 2-(2,6-Dichlorophenyl)-3,8-dihydroimidazo[4,5-d]dipyrido[2,3-b:4',3'-f]azepine dihydrochloride

HRID 75203Notes

Reaction equation

HRID 75203 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[N:10](O)[C:11]2[C:17]3[CH:18]=[CH:19][N:20]=[CH:21][C:16]=3[NH:15][C:14]3[N:22]=[CH:23][CH:24]=[CH:25][C:13]=3[C:12]=2[N:26]=1.P(OCC)(OCC)OCC>CN(C)C=O>[ClH:1].[ClH:1].[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[NH:10][C:11]2[C:17]3[CH:18]=[CH:19][N:20]=[CH:21][C:16]=3[NH:15][C:14]3[N:22]=[CH:23][CH:24]=[CH:25][C:13]=3[C:12]=2[N:26]=1

Participants

4

Reactant 2

HCID 31215Triethyl phosphiteHCID 668867982-(2,6-Dichlorophenyl)imidazo[4,5-d]dipyrido[2,3-b:4',3'-f]azepin-3(8H)-ol

Product 1

HCID 668869302-(2,6-Dichlorophenyl)-3,8-dihydroimidazo[4,5-d]dipyrido[2,3-b:4',3'-f]azepine dihydrochlorideYield 241.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(2,6-Dichlorophenyl)imidazo[4,5-d]dipyrido[2,3-b:4′,3′-f]azepin-3(8H)-ol (15.2 g, 0.0384 mol) in N,N-dimethylformamide (250 mL) was treated with triethyl phosphite (26.3 mL, 0.153 mol) and the solution was heated to reflux for 2.5 hours. The solution was allowed to cool to room temperature and was concentrated in vacuo. The residual yellow solid was collected by filtration (using 2 L of acetonitrile to wash). The yellow powder was then dissolved in 250 mL of 0.5 N aqueous hydrochloric acid and 50 mL of acetonitrile. The dark red solution was freeze dried for 16 hours to afford the desired product as an orange-red powder (14.0 g, 85%). 1H NMR (400 MHz, d6-DMSO): δ 8.81 (s, 1H), 8.09 (d, J=6.2 Hz, 1H), 8.03 (s, 1H), 7.94 (dd, J=5.0, 1.6 Hz, 1H), 7.69-7.57 (m, 5H), 6.86 (dd, J=7.5, 4.9 Hz, 1H). LCMS calculated for C19H12Cl2N5 (M+H)+: m/z=380.

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 2.5 hours
  3. concentrationwas concentrated in vacuo
  4. filtrationThe residual yellow solid was collected by filtration (using 2 L of acetonitrile to wash)
  5. dissolutionThe yellow powder was then dissolved in 250 mL of 0.5 N aqueous hydrochloric acid
  6. customdried for 16 hours

Sources & evidence

ORD record
ord-b214cf7d320b41aaa9c6a0a3c5680a30
Source dataset
uspto-grants-2014_09
Patent number
US08835423B2

Reaction notes

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