N,N'-Dimethylethylenediamine → 2,6-dichloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indole

HRID 522751Notes

Reaction equation

[Cl:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[C:6]([Cl:11])[CH:5]=2.Br[C:13]1[CH:14]=[N:15][N:16]([CH2:18][CH2:19][CH3:20])[CH:17]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>C1(C)C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[N:3]([C:13]2[CH:14]=[N:15][N:16]([CH2:18][CH2:19][CH3:20])[CH:17]=2)[C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[C:6]([Cl:11])[CH:5]=2

Participants

Conditions

Temperature: 120 °C

Procedure

To a stirred solution of compound 2 (350 mg, 1.89 mmol) in toluene (10 mL) under inert atmosphere were added 4-bromo-1-propyl-1H-pyrazole (Intermediate B; 422 mg, 2.27 mmol), potassium phosphate (1 g, 4.72 mmol), N,N′-dimethylethylene diamine (66.7 mg, 0.75 mmol) and CuI (36 mg, 0.18 mmol) at RT; heated to 120° C. and stirred for 12 h in a sealed tube. The reaction was monitored by TLC; after completion of the reaction, the volatiles were removed under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 5-7% EtOAc/Hexanes to afford compound 3 (200 mg, 36%) as colorless oil. 1H NMR (500 MHz, CDCl3): δ 7.63 (s, 1H), 7.59 (s, 1H), 7.44 (d, J=9.0 Hz, 1H), 7.14 (s, 1H), 7.11 (d, J=9.0 Hz, 1H), 6.55 (s, 1H), 4.18 (t, J=7.0 Hz, 2H), 2.02-1.97 (m, 2H), 0.98 (t, J=7.5 Hz, 3H); LC-MS (ESI): 59.4%; m/z 294.2 (M+H+); (column: X Select C-18, 50×3.0 mm, 3.5 μm); RT 4.66 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

customafter completion of the reaction
customthe volatiles were removed under reduced pressure
customto obtain the crude
customThis was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-7b74d68ceea94640adc22e3067283194
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334261B2

Reaction notes

Loading…