Acetic Acid → HCID 70896181, compound

HRID 2369859Notes

Reaction equation

HRID 2369859 reaction equation
C(O[CH2:5][C:6]1[CH:14]=[CH:13][C:12]2[CH2:15][NH:16][C@@H:17]([CH:20]3[CH:25]4[CH2:26][CH2:27][N:22]([CH2:23][CH2:24]4)[CH2:21]3)[C:18](=[O:19])[N:10]3[C:11]=2[C:7]=1[CH:8]=[CH:9]3)(=O)C.C(O)(=O)C>CO.[Pd]>[CH3:5][C:6]1[CH:14]=[CH:13][C:12]2[CH2:15][NH:16][C@@H:17]([CH:20]3[CH:25]4[CH2:24][CH2:23][N:22]([CH2:27][CH2:26]4)[CH2:21]3)[C:18](=[O:19])[N:10]3[C:11]=2[C:7]=1[CH:8]=[CH:9]3

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 70896273HCID 70896273, compound

Product 1

HCID 70896181HCID 70896181, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(S)-(1-Oxo-2-(quinuclidin-3-yl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)methyl acetate (124 mg, 0.34 mmol) from Step C above was dissolved in methanol (7 ml) and glacial acetic acid (3 ml). Excess 10% palladium on carbon was added and the suspension was stirred under an atmosphere of hydrogen (balloon pressure) overnight. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure and purified by column chromatography (silica gel, 90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide) and preparative TLC (90:10:10 methylene chloride/methanol/concentrated ammonium hydroxide) to afford (S)-7-methyl-2-(quinuclidin-3-yl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-1(2H)-one. This material was dissolved in methanol and treated with HCl (1.25 M solution in methanol) and the mixture was concentrated under reduced pressure. The residue was lyophilized from water to afford (S)-7-methyl-2-(quinuclidin-3-yl)-3,4-dihydro-[1,4]diazepino[6,7,1-hi]indol-1(2H)-one hydrochloride (100 mg, 85%) as a white solid: 1H NMR (500 MHz, CD3OD) δ 7.80 (d, J=4.0 Hz, 1H), 7.75 (d, J=3.8 Hz, 1H), 7.17 (t, J=8.0 Hz, 1H), 7.17 (t, J=8.0 Hz, 1H), 4.90 (s, 1H), 4.22 (br s, 1H), 4.11 (br s, 1H), 3.77-3.72 (m, 2H), 3.48-3.29 (m, 6H), 2.35 (d, J=8.0 Hz, 1H), 2.21 (s, 3H), 2.06-1.96 (m, 4H); MS (ESI+) m/z 310 (M+H).

Workup

  1. filtrationThe suspension was filtered through Celite
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. custompurified by column chromatography (silica gel, 90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide) and preparative TLC (90:10:10 methylene chloride/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-9914a7b971a74792b35b96e7c4682152
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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