Hydrochloric Acid → HCID 44624069, compound

HRID 2274042Notes

Reaction equation

HRID 2274042 reaction equation
[CH:1]([O:4][C:5]1[N:6]=[CH:7][C:8]([CH2:11][O:12][C:13]2[CH:21]=[CH:20][C:19]3[NH:18][C:17]4[CH:22]([CH2:25][C:26]([O:28]CC)=[O:27])[CH2:23][CH2:24][C:16]=4[C:15]=3[CH:14]=2)=[N:9][CH:10]=1)([CH3:3])[CH3:2].[Li+].[OH-].O.Cl>O1CCOCC1>[CH:1]([O:4][C:5]1[N:6]=[CH:7][C:8]([CH2:11][O:12][C:13]2[CH:21]=[CH:20][C:19]3[NH:18][C:17]4[CH:22]([CH2:25][C:26]([OH:28])=[O:27])[CH2:23][CH2:24][C:16]=4[C:15]=3[CH:14]=2)=[N:9][CH:10]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium Hydroxide2×HCID 67220693HCID 67220693, compound

Product 1

HCID 44624069HCID 44624069, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Ethyl 2-(7-hydroxy-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (0.035 g, 0.135 mmol) and cesium carbonate (0.048 g, 0.148 mmol) were dissolved in DMF (0.5 mL) and stirred at room temperature for 5 min. To this mixture at 0° C. was added a solution of 2-(bromomethyl)-5-isopropoxypyrazine (0.034 g, 0.148 mmol) in DMF (0.20 mL) and was stirred at room temperature for 60 h. The solids were removed by filtration. The filtrate was purified by HPLC to give ethyl 2-(7-((5-isopropoxypyrazin-2-yl)methoxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (11 mg). To the ester dissolved in dioxane (288 μL) was added aqueous LiOH (1 N, 72 μL). The mixture was stirred at room temperature for 16 h; before more aqueous LiOH (1 N, 200 μL) was added. Stirring was continued for 1 h. To the reaction mixture was added water (1.5 mL) and the reaction mixture was acidified to pH 3 with 1 N HCl. The mixture was purified by HPLC to give the title compound as a yellow solid (7 mg). LCMS m/z=382.4 [M+H]+; 1H NMR (500 MHz, CDCl3) δ ppm 1.32 (d, J=6.31 Hz, 6H), 1.95-2.18 (m, 1H), 2.28-2.41 (m, 1H), 2.56-2.79 (m, 4H), 3.36-3.56 (m, 1H), 5.09 (s, 2H), 5.15-5.33 (m, 1H), 6.71 (d, J=8.83 Hz, 1H), 6.94 (s, 1H), 7.20 (d, J=8.83 Hz, 1H), 8.20 (s, 1H), 8.30 (s, 1H), 10.37 (s, 1H).

Workup

  1. stirringStirring
  2. waitwas continued for 1 h
  3. customThe mixture was purified by HPLC

Sources & evidence

ORD record
ord-13c1dc103e3d4588b58ec61745eb66c2
Source dataset
uspto-grants-2015_09
Patent number
US09126932B2

Reaction notes

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