Hydrogen Bromide → 2-(4-Hydroxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride

HRID 2036689Notes

Reaction equation

HRID 2036689 reaction equation
[ClH:1].C[O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH3:22])[C:17]2[CH2:23][CH:24]4[NH:28][CH:27]([C:16]3=2)[CH2:26][CH2:25]4)(=[O:12])=[O:11])=[CH:6][CH:5]=1.Br>C(O)(=O)C>[ClH:1].[OH:3][C:4]1[CH:5]=[CH:6][C:7]([S:10]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH3:22])[C:17]2[CH2:23][CH:24]4[NH:28][CH:27]([C:16]3=2)[CH2:26][CH2:25]4)(=[O:12])=[O:11])=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 529129802-(4-Methoxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride

Product 1

HCID 529129822-(4-Hydroxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochlorideYield 12.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of the product of Example 31, step B (18 mg, 0.04 mmol) and 33% HBr in acetic acid (10 mL) was heated at 60° C. for 4 days. The reaction mixture was concentrated in vacuo and the resulting residue neutralized with saturated sodium bicarbonate solution before extracting with dichloromethane. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by semi-preparative HPLC and the free base treated with 1.25 M HCl methanol solution (0.5 mL) to give 2-(4-hydroxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride (2 mg, 12%, AUC HPLC 97.2%) as an off-white solid: mp 210-212° C.; 1H NMR (CD3OD, 300 MHz) δ 8.18-8.23 (m, 1H), 7.73-7.81 (m, 2H), 7.69 (dd, J=9.0 Hz, 1.8 Hz, 1H), 7.55 (d, J=8.7 Hz, 1H), 6.82-6.90 (m, 2H), 5.25-5.36 (m, 1H), 4.53 (br s, 1H), 3.71 (s, 3H), 3.40-3.55 (m, 1H), 3.46-3.55 (m, 1H), 3.01-3.11 (m, 1H), 2.23-2.51 (m, 2H), 1.92-2.11 (m, 1H); ESI MS m/z 369 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. extractionbefore extracting with dichloromethane
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by semi-preparative HPLC
  7. additionthe free base treated with 1.25 M HCl methanol solution (0.5 mL)

Sources & evidence

ORD record
ord-22ef8d0008b442e390558a2d897c89be
Source dataset
uspto-grants-2013_11
Patent number
US08575186B2

Reaction notes

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