Hydrochloric Acid → Hydrochloric Acid

HRID 2040744Notes

Reaction equation

HRID 2040744 reaction equation
S1(CCCC1)(=O)=O.[NH2:8][C:9]1[N:14]=[C:13]([NH2:15])[C:12]([O:16][C:17]2[C:18]([CH:29]([CH3:31])[CH3:30])=[CH:19][C:20]([O:27][CH3:28])=[C:21]([S:23]([NH2:26])(=[O:25])=[O:24])[CH:22]=2)=[CH:11][N:10]=1.[ClH:32]>C(O)C>[ClH:32].[NH2:8][C:9]1[N:14]=[C:13]([NH2:15])[C:12]([O:16][C:17]2[C:18]([CH:29]([CH3:31])[CH3:30])=[CH:19][C:20]([O:27][CH3:28])=[C:21]([S:23]([NH2:26])(=[O:24])=[O:25])[CH:22]=2)=[CH:11][N:10]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86619554HCID 86619554, compound

Product 2

HCID 313Hydrochloric AcidHCID 24764487Gefapixant

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A slurry of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide sulfolane solvate (23.86 kg) in a mixture of ethanol (74.3 kg) and 0.44 N HCl (109.4 kg) was heated to reflux to provide a homogeneous solution of the monohydrochloride salt of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide. This solution was filtered while hot, then treated with concentrated ammonium hydroxide (3.4 L) to liberate the free base of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide. The resultant mixture was cooled slowly to 20 degrees C. and the crystalline product isolated by filtration. The filter cake was washed with water (20.1 kg) and dried under reduced pressure at 70 degrees C. to a constant weight of 8.17 kg (57.7% yield based on di-solvate of sulfolane). MP=281-282° C. 1H nmr (DMSO-d6) delta: 1.27 (d, 6H, J=6.9 Hz), 3.41 (septet, 1H, J=6.9 Hz), 3.89 (s, 3H), 5.87 (s (br), 2H), 6.40 (s (br), 2H), 6.98 (s, 1H), 7.01 (s (br), 2H), 7.07 (s, 1H), 7.36 (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux

Sources & evidence

ORD record
ord-034f2d953ecb4e7898e64c00050dee2f
Source dataset
uspto-grants-2013_11
Patent number
US08580960B2

Reaction notes

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