Hydrochloric Acid → 2,3,4,5-Tetrahydro-8-methoxy-6-(trifluoromethyl)-1H-pyrido[4,3-b]indole

HRID 2215915Notes

Reaction equation

HRID 2215915 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10]N)=[C:6]([C:12]([F:15])([F:14])[F:13])[CH:5]=1.Cl.O.[NH:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.Cl>>[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:12]([F:15])([F:14])[F:13])[C:7]2[NH:10][C:21]3[CH2:22][CH2:23][NH:18][CH2:19][C:20]=3[C:8]=2[CH:9]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 2723901PiperonylamineHCID 21952658HCID 21952658, compound

Product 1

HCID 160663982,3,4,5-Tetrahydro-8-methoxy-6-(trifluoromethyl)-1H-pyrido[4,3-b]indoleYield 42%

Procedure

A microwave-compatible seal tube was charged with (4-methoxy-2-trifluoromethyl-phenyl)-hydrazine hydrochloride (406 mg, 1.7 mmol), 4-piperidone monohydrate hydrochloride (268 mg, 1.7 mmol), and 2-PrOH (4 mL). The reaction mixture was saturated with HCl gas and the tube was sealed. The reaction mixture was subjected to microwave irradiation at 120° C. for 12 min. The solids were filtered, washed with ether and treated with sat. NaHCO3 (10 mL). The basic solution was extracted with EtOAc (2×25 mL) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue by column chromatography [silica gel, 5–75% (80:18:2 CHCl3/MeOH/concd NH4OH)/CH2Cl2] provided 8-methoxy-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (192 mg, in 42%) as an off-white solid: mp 140–144° C.; 1H NMR (300 MHz, CD3OD) δ 7.10 (d, J=2.0 Hz, 1H), 6.93 (d, J=2.1 Hz, 1H), 3.97 (s, 2H), 3.83 (s, 3H), 3.16 (t, J=5.8 Hz, 2H), 2.87 (t, J=5.7 Hz, 2H); 19F NMR (282 MHz, CD3OD) δ −61.0; ESI MS 271 [C13H13F3N2O+H]+.

Workup

  1. customthe tube was sealed
  2. customirradiation at 120° C. for 12 min
  3. filtrationThe solids were filtered
  4. washwashed with ether
  5. additiontreated with sat. NaHCO3 (10 mL)
  6. extractionThe basic solution was extracted with EtOAc (2×25 mL)
  7. dry with materialthe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification of the residue by column chromatography [silica gel, 5–75% (80:18:2 CHCl3/MeOH/concd NH4OH)/CH2Cl2]

Sources & evidence

ORD record
ord-68e46154040a469c905d2a7063a80acc
Source dataset
uspto-grants-2006_09
Patent number
US07109339B2

Reaction notes

Loading…