Triethylamine → HCID 58833670, compound

HRID 2203557Notes

Reaction equation

HRID 2203557 reaction equation
[CH3:1][S:2]([O:5]S(C)(=O)=O)(=O)=[O:3].[NH2:10][C:11]1[C:20]2[N:21]=[C:22]([CH2:35][O:36][CH2:37][CH3:38])[N:23]([CH2:24][C:25]([NH:28][C:29]([NH:31][CH:32]([CH3:34])[CH3:33])=[O:30])([CH3:27])[CH3:26])[C:19]=2[C:18]2[CH:17]=[CH:16][C:15]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH2:46])=[CH:14][C:13]=2[N:12]=1.C(N(CC)CC)C>ClCCl>[NH2:10][C:11]1[C:20]2[N:21]=[C:22]([CH2:35][O:36][CH2:37][CH3:38])[N:23]([CH2:24][C:25]([NH:28][C:29]([NH:31][CH:32]([CH3:34])[CH3:33])=[O:30])([CH3:26])[CH3:27])[C:19]=2[C:18]2[CH:17]=[CH:16][C:15]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH:46][S:2]([CH3:1])(=[O:5])=[O:3])=[CH:14][C:13]=2[N:12]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 81560Methanesulfonic anhydride2×HCID 69507030HCID 69507030, compound

Product 1

HCID 58833670HCID 58833670, compoundYield 29.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonic anhydride (0.34 g, 1.93 mmol) was added to a stirred solution of N-{2-[4-amino-7-[(6-aminohexyl)oxy]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}-N′-isopropylurea (prepared as described in Parts A-H of Example 369, 10.9 g, 1.75 mmol) and triethylamine (0.35 mL, 3.5 mmol) in dichloromethane (50 mL) at 0° C. After approximately 30 minutes, the solution was allowed to warm to room temperature and was stirred overnight. The following morning, the solution was cooled to 0° C. and additional methanesulfonic anhydride (0.13 g) was added. After 30 minutes, the solution was allowed to warm to room temperature. After 2 hours, the solution was transferred to a separatory funnel and washed with water (2×) and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, elution with 10% methanol in dichloromethane) followed purification by chromatography on a HORIZON HPFC system (an automated, modular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va., USA) (silica gel, gradient elution with 0-40% CMA in chloroform where CMA is a solution of 80:18:2 chloroform/methanol/concentrated ammonium hydroxide) to yield 0.31 g of N-(6-{[4-amino-2-(ethoxymethyl)-1-(2-{[(isopropylamino)carbonyl]amino}-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]oxy}hexyl)methanesulfonamide as an off white solid, mp 190-194° C.

Workup

  1. temperatureThe following morning, the solution was cooled to 0° C.
  2. waitAfter 30 minutes
  3. temperatureto warm to room temperature
  4. waitAfter 2 hours
  5. customthe solution was transferred to a separatory funnel
  6. washwashed with water (2×) and brine
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by flash chromatography (silica gel, elution with 10% methanol in dichloromethane)
  11. custompurification by chromatography on a HORIZON HPFC system (
  12. custommodular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va
  13. wash, USA) (silica gel, gradient elution with 0-40% CMA in chloroform where CMA

Sources & evidence

ORD record
ord-ee2c32028c554c31a944ac4bc1a1f6b8
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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