Isoquinoline-5-sulfonyl chloride hydrochloride → N5-[4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-isoquinolinesulfonamide

HRID 1795918Notes

Reaction equation

HRID 1795918 reaction equation
Cl.[CH:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([S:12](Cl)(=[O:14])=[O:13])[C:6]=2[CH:5]=[CH:4][N:3]=1.[NH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]1[C:33]2[C:32]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[N:26]=[C:25]([NH2:34])[C:24]=2[N:23]=[C:22]1[CH2:35][CH2:36][CH2:37][CH3:38]>ClCCl>[NH2:34][C:25]1[C:24]2[N:23]=[C:22]([CH2:35][CH2:36][CH2:37][CH3:38])[N:21]([CH2:20][CH2:19][CH2:18][CH2:17][NH:16][S:12]([C:7]3[C:6]4[CH:5]=[CH:4][N:3]=[CH:2][C:11]=4[CH:10]=[CH:9][CH:8]=3)(=[O:14])=[O:13])[C:33]=2[C:32]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[N:26]=1

Participants

4

Reactant 2

HCID 13116932Isoquinoline-5-sulfonyl chloride hydrochloride2×HCID 155382261-(4-Aminobutyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 10117950N5-[4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-isoquinolinesulfonamideYield 44.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of isoquinoline-5-sulfonyl chloride hydrochloride (0.83 g in 50 ml of pyridine, 3.1 mmol) was added dropwise to a stirring solution of 1-(4-aminobutyl)-2-butyl-1H-imidazo[4,5-c]quinoline-4-amine (1.0 g, 3.2 mmol) and dichloromethane (175 ml). The solution turned a bright yellow color and was maintained at room temperature for 4 hours. An additional 0.18 g of isoquinoline-5-sulfonyl chloride hydrochloride was added and the reaction was maintained an additional 60 hours. The yellow solution was concentrated in vacuo, dissolved in dichloromethane, and washed sequentially with saturated aqueous sodium bicarbonate and water. The organic fraction was dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 9:1 dichloromethane\methanol) to provide 0.7 g of N5-[4-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-5-isoquinolinesulfonamide as a white crystalline solid, m.p. 96.0° C. (decomposition). 1H NMR (300 MHz, DMSO-d6) δ 9.44 (d, J=0.7 Hz, 1H), 8.64(d, J=6.1 Hz, 1H), 8.41–8.35 (m, 2H), 8.30 (dd, J=7.4, 1.2 Hz, 1H), 8.11 (t, J=5.6 Hz, 1H), 7.92 (d, J=7.6 Hz, 1H), 7.75 (t, J=7.7 Hz, 1H), 7.61 (dd, J=8.3, 1.2 Hz, 1H), 7.41 (dt, J=7.7, 1.2 Hz, 1H), 7.22 (dt, J=7.6, 1.2 Hz, 1H), 6.47 (broad s, 2H), 4.38 (t, J=7.5 Hz, 2H), 2.86–2.74 (m, 4H), 1.78–1.63 (m, 4H), 1.50–1.34 (m, 4H), 0.94 (t, J=7.4 Hz, 3H); MS (EI) m/e 502.2151 (502.2151 calcd for C27H30N6O2S). Anal calcd for C27H30N6O2S: C, 64.52; H, 6.02; N, 16.72. Found: C, 64.03; H, 6.03; N, 16.55.

Workup

  1. temperaturethe reaction was maintained an additional 60 hours
  2. concentrationThe yellow solution was concentrated in vacuo
  3. dissolutiondissolved in dichloromethane
  4. washwashed sequentially with saturated aqueous sodium bicarbonate and water
  5. dry with materialThe organic fraction was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography (silica gel, 9:1 dichloromethane\methanol)

Sources & evidence

ORD record
ord-ee205c2918e14bab96784284a6a09971
Source dataset
uspto-grants-2006_04
Patent number
US07030131B2

Reaction notes

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