Methanesulfonic Acid → Taprizosin mesylate

HRID 1840760Notes

Reaction equation

HRID 1840760 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH3:21])=[C:9]([O:18][CH3:19])[C:10]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[N:5]=[C:4]([N:22]2[CH2:31][CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[CH2:23]2)[N:3]=1.[CH3:37][S:38]([OH:41])(=[O:40])=[O:39]>CC(=O)CC.O>[S:38]([OH:41])(=[O:40])(=[O:39])[CH3:37].[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH3:21])=[C:9]([O:18][CH3:19])[C:10]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[N:5]=[C:4]([N:22]2[CH2:31][CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[CH2:23]2)[N:3]=1

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 6433102Taprizosin

Product 1

HCID 9830194Taprizosin mesylateYield 92.5%

Reagents, catalysts & solvents 1

HCID 19370624Water 2-butanoneSolvent2×

Conditions

Temperature
50 °C

Procedure

Under nitrogen, a suspension of Form B 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline (2.0 g) in butanone/water (10/1 by volume, 24 ml) was heated to reflux over 20 mins. Butanone/water 10/1 was added until a solution was achieved (an extra 3 ml was added, bringing the total solvent volume to 27 ml). The solution was left to cool to 50° C. and methanesulfonic acid (0.38 g, 4.0 mmol) was added dropwise over 30 seconds. The addition vessel was washed with butanone/water 10/1 (2×0.25 ml) and the washings were added to the reaction vessel. The resulting suspension was left to cool to room temperature and then stirred at this temperature for 2 h. The solid was collected by filtration, washed with acetone (2×2 ml), left to pull dry for 30 min and dried overnight in vacuo at 54° C. to afford the title compound (2.2 g) as a white solid.

Workup

  1. temperaturewas heated
  2. temperatureto reflux over 20 mins
  3. additionwas added
  4. waitThe solution was left
  5. washThe addition vessel was washed with butanone/water 10/1 (2×0.25 ml)
  6. additionthe washings were added to the reaction vessel
  7. waitThe resulting suspension was left
  8. temperatureto cool to room temperature
  9. filtrationThe solid was collected by filtration
  10. washwashed with acetone (2×2 ml)
  11. waitleft
  12. customto pull dry for 30 min
  13. customdried overnight in vacuo at 54° C.

Sources & evidence

ORD record
ord-cea4e37109f4430681d0b61554a949f0
Source dataset
uspto-grants-2004_01
Patent number
US06683085B2

Reaction notes

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