Benzenesulfonyl chloride → Sotirimod

HRID 2090172Notes

Reaction equation

HRID 2090172 reaction equation
[OH-].[NH4+:2].[CH3:3][C:4]1[N:5]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:6]2[C:15]3[N:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N+:9]([O-])=[CH:8][C:7]=2[N:17]=1.C1(S(Cl)(=O)=O)C=CC=CC=1.[OH-].[Na+]>CO.O>[CH3:3][C:4]1[N:5]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:6]2[C:15]3[N:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[C:8]([NH2:2])[C:7]=2[N:17]=1

Participants

7

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 66618079HCID 66618079, compound

Product 1

HCID 6450818Sotirimod

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

Under a nitrogen atmosphere, aqueous ammonium hydroxide (four equivalents) was quickly added with continuous stirring to a suspension of 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-5-oxide in methanol (6 mL/g) while maintaining the reaction temperature at 20° C. to 24° C. Methanol was used to rinse the addition vessel and added to the reaction. The reaction was stirred until all material was dissolved. With continuous stirring, benzenesulfonyl chloride (2 equivalents) was added over a period of 15 to 45 minutes while maintaining the reaction temperature at 20° C. to 30° C. Methanol was used to rinse the addition vessel and added to the reaction. The reaction was stirred for 45 to 75 minutes at 20° C. to 24° C. Aqueous sodium hydroxide (3 equivalents of 10% w/w) was added to the reaction mixture over a period of 15 to 45 minutes while maintaining the reaction temperature between 20° C. and 25° C. Water (10 L), used to rinse the addition vessel, was added to the reaction mixture. The resulting mixture was cooled to 10° C. and stirred for 2 to 24 hours. A precipitate was present and was isolated by filtration and washed with deionized water until the filtrate was pH 7. The solid was dried at 50° C. under vacuum to provide 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine as an off-white solid.

Workup

  1. temperaturewhile maintaining the reaction temperature at 20° C. to 24° C
  2. washto rinse the addition vessel
  3. additionadded to the reaction
  4. dissolutionwas dissolved
  5. temperaturewhile maintaining the reaction temperature at 20° C. to 30° C
  6. washto rinse the addition vessel
  7. additionadded to the reaction
  8. stirringThe reaction was stirred for 45 to 75 minutes at 20° C. to 24° C
  9. temperaturewhile maintaining the reaction temperature between 20° C. and 25° C
  10. washto rinse the addition vessel
  11. additionwas added to the reaction mixture
  12. stirringstirred for 2 to 24 hours
  13. customwas isolated by filtration
  14. washwashed with deionized water until the filtrate
  15. customThe solid was dried at 50° C. under vacuum

Sources & evidence

ORD record
ord-585c6d959aa946769e565230e9baf3bf
Source dataset
uspto-grants-2013_05
Patent number
US08436176B2

Reaction notes

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