Dichloromethane → N-{3-[(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)amino]propyl}-3-mercaptopropanamide

HRID 1845719Notes

Reaction equation

HRID 1845719 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][CH2:5][NH: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[CH3:21].C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[S:29][CH2:30][CH2:31][C:32](ON2C(=O)CCC2=O)=[O:33])C=CC=CC=1.C(N(CC)CC)C.ClCCl>CO>[NH2:20][C:11]1[C:10]2[N:9]=[C:8]([CH3:21])[N:7]([NH:6][CH2:5][CH2:4][CH2:3][NH:2][C:32](=[O:33])[CH2:31][CH2:30][SH:29])[C:19]=2[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 179354262,5-Dioxopyrrolidin-1-yl 3-(tritylthio)propanoateHCID 86626929N1-(3-aminopropyl)-2-methyl-1H-imidazo[4,5-c]quinoline-1,4-diamine hydrochloride

Product 1

HCID 57568669N-{3-[(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)amino]propyl}-3-mercaptopropanamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of N1-(3-aminopropyl)-2-methyl-1H-imidazo[4,5-c]quinoline-1,4-diamine hydrochloride (1.00 g, 3.26 mmol), succinimido 3-(triphenylmethylthio)propanoate (A. Bray et. al. Aust. J. Chem. 1990, 43, 629-634; 2.22 g, 4.89 mmol), triethylamine (0.45 mL, 3.26 mmol), dichloromethane (33 mL), and methanol (15 mL) was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel (gradient elution with a solution of 2% ammonium hydroxide in methanol and chloroform). The purified compound was treated with trifluoroacetic acid (3 mL) and triethylsilane (2 mL) in dichloromethane (30 mL) at room temperature overnight. More trifluoroacetic acid was added and after an additional day the reaction was complete. The reaction mixture was concentrated under reduced pressure and purified by flash chromatography on silica gel (gradient elution with a solution of 2% ammonium hydroxide in methanol and chloroform) to yield 327 mg of N-{3-[(4-amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)amino]propyl}-3-mercaptopropanamide. MS (ESI) m/z 359 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by flash chromatography on silica gel (
  3. washgradient elution with a solution of 2% ammonium hydroxide in methanol and chloroform)
  4. additionThe purified compound was treated with trifluoroacetic acid (3 mL) and triethylsilane (2 mL) in dichloromethane (30 mL) at room temperature overnight
  5. additionMore trifluoroacetic acid was added and after an additional day the reaction
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. custompurified by flash chromatography on silica gel (
  8. washgradient elution with a solution of 2% ammonium hydroxide in methanol and chloroform)

Sources & evidence

ORD record
ord-1f25219a32614524821707a7c932a533
Source dataset
uspto-grants-2015_02
Patent number
US08951528B2

Reaction notes

Loading…