Trifluoroacetic acid → N-{6-[(4-amino-2-(ethoxymethyl)-1-{2-methyl-2-[(methylsulfonyl)amino]propyl}-1H-imidazo[4,5-c]quinolin-7-yl)oxy]hexyl}-3-mercaptopropanamide

HRID 1845724Notes

Reaction equation

HRID 1845724 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:31][O:32][CH2:33][CH3:34])[N:21]([CH2:22][C:23]([CH3:30])([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH3:24])[C:17]=2[C:16]2[CH:15]=[CH:14][C:13]([O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:66])[CH2:44][CH2:45][S:46]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:12][C:11]=2[N:10]=1.C([SiH](CC)CC)C>ClCCl>[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:31][O:32][CH2:33][CH3:34])[N:21]([CH2:22][C:23]([CH3:30])([NH:25][S:26]([CH3:29])(=[O:27])=[O:28])[CH3:24])[C:17]=2[C:16]2[CH:15]=[CH:14][C:13]([O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:66])[CH2:44][CH2:45][SH:46])=[CH:12][C:11]=2[N:10]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052Triethylsilane2×HCID 68924374N-{6-[(4-amino-2-(ethoxymethyl)-1-{2-methyl-2-[(methylsulfonyl)amino]propyl}-1H-imidazo[4,5-c]quinolin-7-yl)oxy]hexyl}-3-(tritylthio)propanamide

Product 1

HCID 57568668N-{6-[(4-amino-2-(ethoxymethyl)-1-{2-methyl-2-[(methylsulfonyl)amino]propyl}-1H-imidazo[4,5-c]quinolin-7-yl)oxy]hexyl}-3-mercaptopropanamideYield 3.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1 mL) was added to a 0° C. solution of N-{6-[(4-amino-2-(ethoxymethyl)-1-{2-methyl-2-[(methylsulfonyl)amino]propyl}-1H-imidazo[4,5-c]quinolin-7-yl)oxy]hexyl}-3-(tritylthio)propanamide (0.22 g, 2.63 mmol) and triethylsilane (0.46 mL, 2.89 mmol) in dichloromethane (7 mL). The solution was stirred for 1 hour; then additional triethylsilane (0.05 mL) was added. After an additional hour at 0° C., the solution was concentrated under reduced pressure. The residue was concentrated under reduced pressure from ethyl acetate and toluene. The material was purified by HPFC on silica gel (gradient elution with 25-100% CMA in chloroform) and then subjected to the procedure described in Part D of the synthesis of IRM Compound 1 to provide 51 mg of N-{6-[(4-amino-2-(ethoxymethyl)-1-{2-methyl-2-[(methylsulfonyl)amino]propyl}-1H-imidazo[4,5-c]quinolin-7-yl)oxy]hexyl}-3-mercaptopropanamide, mp 152-157° C. MS (ESI) m/z 595 (M+H)+. Anal. Calcd for C27H42N6O5S2: C, 54.52; H, 7.12; N, 14.13; S, 10.78. Found: C, 54.41; H, 7.13; N, 13.85; S, 10.63.

Workup

  1. waitAfter an additional hour at 0° C.
  2. concentrationthe solution was concentrated under reduced pressure
  3. concentrationThe residue was concentrated under reduced pressure from ethyl acetate and toluene
  4. customThe material was purified by HPFC on silica gel (gradient elution with 25-100% CMA in chloroform)
  5. customdescribed in Part D of the synthesis of IRM Compound 1

Sources & evidence

ORD record
ord-3297c3f3f77c4eb29b1eb06c17317607
Source dataset
uspto-grants-2015_02
Patent number
US08951528B2

Reaction notes

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