Stearic Acid → Telratolimod

HRID 594208Notes

Reaction equation

HRID 594208 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][N:7]1[C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[C:11]([NH2:20])[C:10]=2[N:9]=[C:8]1[CH2:21][CH2:22][CH2:23][CH3:24].[C:25](O)(=[O:43])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42].Cl.C(N=C=NCCCN(C)C)C>ClCCl.CO>[NH2:20][C:11]1[C:10]2[N:9]=[C:8]([CH2:21][CH2:22][CH2:23][CH3:24])[N:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:25](=[O:43])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:19]=2[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1

Participants

6

Reactant 3

HCID 5281Stearic Acid3×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride3×HCID 66765686HCID 66765686, compound

Product 1

HCID 56833311Telratolimod

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

The 1-(4-aminobutoxy)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine was dissolved in dichloromethane (20 mL) and methanol (5 mL). Stearic acid (0.71 g) was added and the reaction was stirred to dissolve the stearic acid. 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC, 0.45 g) was added and the reaction was stirred at ambient temperature for 16 hours. An additional portion of EDC was added (0.23 g) and the reaction was stirred for an additional 24 hours. Final portions of stearic acid (0.22 g) and EDC (0.37 g) were added to drive the reaction to completion and the reaction was stirred at ambient temperature for another 24 hours. The reaction was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography using a Biotage chromatography system (Si40+M2358-1 SiGel column, 85:15 dichloromethane/methanol isocratic elution). The semi-pure product was purified by flash column chromatography two more times using a 90:10 dichloromethane/methanol isocratic elution, followed by a 95:5 dichloromethane/methanol isocratic elution The fractions containing product were concentrated to yield 1.12 g of N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide as an off white waxy solid. 1H-NMR (CDCl3): δ 0.89 (t, 3H), 1.01 (t, 3H), 1.14-1.42 (m, 28H), 1.50 (m, 2H), 1.65 (m, 2H), 1.74-1.94 (m, 4H), 2.02 (m, 2H), 2.20 (t, 2H), 2.95 (t, 2H), 3.40 (q, 2H), 4.33 (t, 2H), 5.59 (t, 1H), 6.10 (broad s, 2H), 7.39 (m, 1H), δ 7.57 (m, 1H), 7.83 (d, 1H), 8.07 (m, 1H).

Workup

  1. stirringthe reaction was stirred at ambient temperature for 16 hours
  2. stirringthe reaction was stirred for an additional 24 hours
  3. customthe reaction to completion
  4. stirringthe reaction was stirred at ambient temperature for another 24 hours
  5. concentrationThe reaction was concentrated under reduced pressure
  6. customthe resulting residue was purified by flash column chromatography
  7. washa Biotage chromatography system (Si40+M2358-1 SiGel column, 85:15 dichloromethane/methanol isocratic elution)
  8. customThe semi-pure product was purified by flash column chromatography two more times
  9. washa 90:10 dichloromethane/methanol isocratic elution
  10. washfollowed by a 95:5 dichloromethane/methanol isocratic elution The fractions
  11. additioncontaining product
  12. concentrationwere concentrated

Sources & evidence

ORD record
ord-6bb35b409d0141f59bc442d6e88a4780
Source dataset
uspto-grants-2016_01
Patent number
US09242980B2

Reaction notes

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