Methanesulfonic Acid → 5,11-Dihydro-11-(((2-(2-((dipropylamino)methyl)-1-piperidinyl)ethyl)amino)carbonyl)-6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one methanesulfonate

HRID 2351398Notes

Reaction equation

HRID 2351398 reaction equation
[CH2:1]([N:4]([CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][N:10]1[CH2:15][CH2:16][NH:17][C:18]([N:20]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[C:24](=[O:31])[NH:23][C:22]2[CH:32]=[CH:33][CH:34]=[N:35][C:21]1=2)=[O:19])[CH2:5][CH2:6][CH3:7])[CH2:2][CH3:3].[CH3:36][S:37]([OH:40])(=[O:39])=[O:38]>C(#N)C.C(OCC)(=O)C>[CH3:36][S:37]([OH:40])(=[O:39])=[O:38].[CH2:1]([N:4]([CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][N:10]1[CH2:15][CH2:16][NH:17][C:18]([N:20]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[C:24](=[O:31])[NH:23][C:22]2[CH:32]=[CH:33][CH:34]=[N:35][C:21]1=2)=[O:19])[CH2:5][CH2:6][CH3:7])[CH2:2][CH3:3]

Participants

5

Reactant 2

HCID 6395Methanesulfonic AcidHCID 119357AF-DX-384

Product 1

HCID 1193565,11-Dihydro-11-(((2-(2-((dipropylamino)methyl)-1-piperidinyl)ethyl)amino)carbonyl)-6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one methanesulfonate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of 56.2 g (0.1174 mol) of 5,11-dihydro-11-[[[2-[2-[(dipropylamino)methyl]-piperidin-1-yl]ethyl]amino]carbonyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one in a mixture of 100 ml of acetonitrile and 100 ml of ethyl acetate, a solution of 11.3 g (0.1176 mol) of methanesulphonic acid in 74 ml of acetonitrile was added dropwise whilst cooling with ice and stirring. After removal of the ice bath the mixture was heated to 70° C., 574 ml of acetic acid were added dropwise to the now clear solution, the mixture was inoculated with a crystal of the desired salt, left to cool to 40° C. and stirred for 2 hours at this temperature, then heated up to 50° C., 280 ml of ethyl acetate were again slowly added dropwise and after removal of the heating bath the mixture was stirred for 2 hours at ambient temperature, left to stand for 14 hours and finally the crystals formed were suction filtered. After washing with ethyl acetate and drying in a circulating air dryer, 64.0 g (95% of theory) of colourless crystals were obtained, m.p. 165°-167° C.

Workup

  1. temperaturewhilst cooling with ice
  2. customAfter removal of the ice bath the mixture
  3. addition574 ml of acetic acid were added dropwise to the now clear solution
  4. waitleft
  5. temperatureto cool to 40° C.
  6. stirringstirred for 2 hours at this temperature
  7. temperatureheated up to 50° C.
  8. addition280 ml of ethyl acetate were again slowly added dropwise
  9. customafter removal of the heating bath the mixture
  10. stirringwas stirred for 2 hours at ambient temperature
  11. waitleft
  12. customfinally the crystals formed
  13. washAfter washing with ethyl acetate
  14. customdrying in a circulating air dryer, 64.0 g (95% of theory) of colourless crystals
  15. customwere obtained

Sources & evidence

ORD record
ord-737295c51b6b4d4ea9fb9ba3f09e39ad
Source dataset
uspto-grants-1989_10
Patent number
US04873236

Reaction notes

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