Ethyl Acetate → HCID 67282556, compound

HRID 1910710Notes

Reaction equation

HRID 1910710 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:36]=[C:35]([Cl:37])[CH:34]=[CH:33][C:10]=3[N:11]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=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:4][CH:3]=1.[Cl-].[Al+3].[Cl-].[Cl-].C(OCC)(=O)C>C1(OC)C=CC=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:36]=[C:35]([Cl:37])[CH:34]=[CH:33][C:10]=3[N:11]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=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:4][CH:3]=1.[NH2:1][C:2]1[N:7]=[CH:6][C:5]([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:4][CH:3]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 67283375HCID 67283375, compound

Product 2

HCID 67282556HCID 67282556, compoundYield 166.5%HCID 67283375HCID 67283375, compound

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Conditions

Temperature
85 °C

Procedure

5-(6-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one was prepared following the procedure for the corresponding reaction in Example 12. 5-(6-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (175 mg, 0.33 mmol) was then dissolved in anhydrous anisole (4 mL), aluminum chloride (263 mg, 1.98 mmol) was added and the mixture was heated to 85° C. for one hour. The solution was cooled to ambient temperature, poured onto ice, and ethyl acetate added then slurried for 10 minutes. The layers were separated, and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with brine, dried with sodium sulfate, decanted and concentrated in vacuo. Column chromatography eluting with a gradient of 0-5% methanol in ethyl acetate provided 5-(6-aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (113 mg, 83% yield). 1H NMR (300 MHz, d6-DMSO) δ 3.44 (m, 2H) 3.72 (m, 1H), 6.40 (m, 1H), 6.48 (s, 2H), 7.18-7.64 (m, 9H), 7.83 (m, 1H), 10.70 (s, 1H); ESI m/z measured 411.0783 [M+H]+. calculated 411.0779.

Workup

  1. customfor the corresponding reaction in Example 12
  2. temperatureThe solution was cooled to ambient temperature
  3. additionadded
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried with sodium sulfate
  8. customdecanted
  9. concentrationconcentrated in vacuo
  10. washColumn chromatography eluting with a gradient of 0-5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-10ea8723bda94610891a6692dcb65e5c
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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