Aluminum(III) Chloride → HCID 22720769, compound

HRID 1582451Notes

Reaction equation

HRID 1582451 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[Cl-].[Cl-].[Al+3].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=O)[C:21](=O)[C:22]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:24]3[CH2:31][CH2:32][NH:33][CH2:34][CH2:35][C:23]=23)=[CH:15][CH:14]=1>C1COCC1>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][CH2:20][CH2:21][C:22]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:24]3[CH2:31][CH2:32][NH:33][CH2:34][CH2:35][C:23]=23)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 9968992HCID 9968992, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 22720769HCID 22720769, compoundYield 82.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1M lithium aluminum hydride (7 mL, 7 mmol) and THF (14 mL) is cooled to 0° C. and portion-wise treated with aluminum trichloride (317 mg, 2.4 mmol) with gas evolution. The resulting colorless solution with a small amount of precipitate is drop-wise treated with a solution of N-(4-methoxyphenyl)-2-oxo-2-(2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)acetamide (433 mg, 1.19 mmol) in THF (10 mL) with additional gas evolution. The resulting yellow suspension is warmed to rt for 20 hr followed by heating to 50° C. for 8 hours. At this time, the reaction is quenched by the successive addition of water (0.27 mL), 5M sodium hydroxide (0.24 mL), and water (0.93 mL). The resulting gelatinous suspension is diluted with dichloromethane, filtered through a pad of celite, with the organics washed once with 1N sodium hydroxide (35 mL), once with brine (35 mL), dried over MgSO4, filtered, and concentrated to give a tan oil. This material is purified by LC (230-400 silica gel) eluting with 5:0.75:94.25 methanol/NH4OH/dichloromethane to afford 330 mg of 4-methoxy-N-[2-(2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)ethyl]aniline as a light golden oil. This material is dissolved in ethyl acetate and treated with 2M hydrochloric acid in methanol (1.1 mL) with immediate formation of a white solid that is collected by filtration and recrystallized from methanol/ethyl acetate to afford 343 mg of 4-methoxy-N-[2-(2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)ethyl]aniline dihydrochloride as a white solid. IR (drift) 2818, 2803, 2746, 2726, 2694, 2669, 2642, 2585, 2552, 2449, 1514, 1471, 1255, 1244, 757 cm−1; OAMS supporting ions at: ESI+ 336.2.

Workup

  1. temperatureby heating to 50° C. for 8 hours
  2. customAt this time, the reaction is quenched by the successive addition of water (0.27 mL), 5M sodium hydroxide (0.24 mL), and water (0.93 mL)
  3. additionThe resulting gelatinous suspension is diluted with dichloromethane
  4. filtrationfiltered through a pad of celite
  5. washwith the organics washed once with 1N sodium hydroxide (35 mL), once with brine (35 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a tan oil
  10. customThis material is purified by LC (230-400 silica gel)
  11. washeluting with 5:0.75:94.25 methanol/NH4OH/dichloromethane

Sources & evidence

ORD record
ord-e7d892aabf6b41028a57d40e31e565f2
Source dataset
uspto-grants-2004_05
Patent number
US06734301B2

Reaction notes

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