4-Toluenesulfonyl chloride → HCID 58833659, compound

HRID 2203604Notes

Reaction equation

HRID 2203604 reaction equation
[CH2:1]([C:3]1[N:4]([CH2:28][CH:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[C:5]2[C:14]3[CH:13]=[CH:12][C:11]([O:15][CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:10][C:9]=3[N+:8]([O-])=[CH:7][C:6]=2[N:27]=1)[CH3:2].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[OH-].[NH4+:47]>ClCCl>[NH2:47][C:7]1[C:6]2[N:27]=[C:3]([CH2:1][CH3:2])[N:4]([CH2:28][CH:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[C:5]=2[C:14]2[CH:13]=[CH:12][C:11]([O:15][CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[CH:10][C:9]=2[N:8]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 68973958HCID 68973958, compound

Product 1

HCID 58833659HCID 58833659, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 2-{[2-ethyl-5-oxido-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]oxy}ethylcarbamate (wet from above) was slurried in dichloromethane (25 mL) and ammonium hydroxide (25 mL). p-Toluenesulfonyl chloride (0.810 g, 4.25 mmol) was added in one portion and the reaction was stirred for 16 hours. The layers were separated and the aqueous fraction was extracted with dichloromethane. The combined organic fractions were washed with water, then saturated aqueous sodium chloride. The organic fraction was dried over anhydrous sodium sulfate, filtered and concentrated. The material was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 2-20% CMA in chloroform) to afford 1.8 g of tert-butyl 2-{[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]oxy}ethylcarbamate as a white foam. Recrystallization from acetonitrile of a small portion provided an analytical sample as a white solid, mp 200-201° C.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous fraction was extracted with dichloromethane
  3. washThe combined organic fractions were washed with water
  4. dry with materialThe organic fraction was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 2-20% CMA in chloroform)

Sources & evidence

ORD record
ord-db90fa6b139d49ffbf2ce466c4863411
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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