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

HRID 2417174Notes

Reaction equation

HRID 2417174 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 vacua. 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 vacua
  8. customThe residue was purified by flash column chromatography (silica gel, 9:1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-c5e36d27a1f74e11a3398245dcf093a1
Source dataset
uspto-grants-2004_11
Patent number
US06825350B2

Reaction notes

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