Triethylamine → HCID 69078773, compound

HRID 2404983Notes

Reaction equation

HRID 2404983 reaction equation
[I:1][C:2]1[CH:7]=[N:6][CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[CH2:15]([C:17]1[N:18]([CH2:31][C:32]#[CH:33])[C:19]2[C:28]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N:22]=[C:21]([NH2:29])[C:20]=2[N:30]=1)[CH3:16]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].[Cu]I>[IH:1].[CH2:15]([C:17]1[N:18]([CH2:31][C:32]#[C:33][C:2]2[CH:7]=[N:6][CH:5]=[CH:4][N:3]=2)[C:19]2[C:28]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N:22]=[C:21]([NH2:29])[C:20]=2[N:30]=1)[CH3:16]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 642841IodopyrazineHCID 86626642HCID 86626642, compound

Product 1

HCID 69078773HCID 69078773, compoundYield 5.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 6228DimethylformamideSolvent

Procedure

Tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (0.12 mg, 0.03 eq.), 2-iodopyrazine (0.90 g, 1.1 eq), triethylamine (1.21 g, 3 eq.), and copper (I) iodide (46 mg, 0.06 eq.) were added sequentially to a solution of 2-ethyl-1-(2-propynyl)-1H-imidazo[4,5-c]quinolin-4-amine (1 g, 4 mmol, 1.0 eq.) in DMF. The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was concentrated under reduced pressure to provide crude product which was purified by column chromatography (silica gel eluting with 8/92 methanol/dichloromethane). The residue was purified by recrystallization from DMF to provide 100 mg of 2-ethyl-1-[3-(pyrazin-2-yl)-2-propynyl]-1H-imidazo[4,5-c]quinolin-4-amine hydroiodide as tan granules, mp 180-225° C. (dec). 1H NMR (300 MHz, DMSO-d6) δ 13.31 (s, 1H), 8.70 (br s, 2H), 8.68 (d, J=1.4 Hz, 1H), 8.61 (m, 2H), 8.48 (dd, J=8.2, 0.9 Hz, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.73 (m, 1H), 7.62 (m, 1H), 5.93 (s, 2H), 3.14 (q, J=7.4 Hz, 2H), 1.43 (t, J=7.4 Hz, 3H); MS (APCI) m/z 329 (M+H)+; Anal. calcd. for C19H16N6.HI.0.06 DMF: C, 50.01; H, 3.81; N, 18.43. Found: C, 49.96; H, 3.84; N, 18.15.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto provide crude product which
  3. customwas purified by column chromatography (silica gel eluting with 8/92 methanol/dichloromethane)
  4. customThe residue was purified by recrystallization from DMF

Sources & evidence

ORD record
ord-38f18f14ebef4cd6b225a46176f102f1
Source dataset
uspto-grants-2014_08
Patent number
US08802853B2

Reaction notes

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