Aluminum(III) Chloride → 5-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 1910673Notes

Reaction equation

HRID 1910673 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[CH:36]=[C:35]([Cl:37])[CH:34]=[CH:33][C:10]=3[N:11](CC3C=CC(OC)=CC=3)[C:12](=[O:23])[CH:13]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])[N:14]=2)[CH:5]=[N:6][CH:7]=1.[Cl-].[Al+3].[Cl-].[Cl-]>C1(OC)C=CC=CC=1>[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[CH:36]=[C:35]([Cl:37])[CH:34]=[CH:33][C:10]=3[NH:11][C:12](=[O:23])[CH:13]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])[N:14]=2)[CH:5]=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 672834995-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Product 1

HCID 672833865-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 34%

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Conditions

Temperature
85 °C

Procedure

5-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (90 mg) was dissolved in anisole (5 mL) and aluminum chloride (90 mg, 4 eq) was then added. The suspension was heated to 85° C. under nitrogen gas for two hours, and then it was cooled to room temperature and poured onto ice water/EtOAc 1:1 (30 mL:30 g). The slurry was stirred vigorously for 1 hour, and the organic phase was then separated and washed with brine. The organic phase was dried over sodium sulfate, then concentrated, and purified by chromatography (gradient: DCM to 8:2 DCM:MeOH) delivering the title compound as a solid (23 mg, 34% yield). 1H-NMR (300 MHz, DMSO-d6) δ 10.80 (s, 1H), 7.98 (d, 1H), 7.65 (m, 2H), 7.47 (dd, 2H), 7.30-7.20 (m, 4H), 6.85 (s, 1H) 5.47 (bs, 2H), 3.77 (t, 1H), 3.45 (d, 2H). HRMS (ES+) m/z calcd for C21H16Cl2N4O [M+H]+, 411.0779. found, 411.0770.

Workup

  1. temperatureit was cooled to room temperature
  2. additionpoured onto ice water/EtOAc 1:1 (30 mL:30 g)
  3. customthe organic phase was then separated
  4. washwashed with brine
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by chromatography (gradient: DCM to 8:2 DCM:MeOH)

Sources & evidence

ORD record
ord-4d4950970aea49ae8da26245018c57e1
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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