p-Toluenesulfonic acid → Cyclopropanecarboxamide, N-((4-((8-chloro-4,10-dihydro-1-methylpyrazolo(3,4-b)(1,5)benzodiazepin-5(1H)-yl)carbonyl)-2-fluorophenyl)methyl)-, 4-methylbenzenesulfonate

HRID 1521460Notes

Reaction equation

HRID 1521460 reaction equation
[S:1]([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)([O-:4])(=[O:3])=[O:2].[Cl:12][C:13]1[CH:14]=[CH:15][C:16]2[N:25]([C:26]([C:28]3[CH:40]=[CH:39][C:31]([CH2:32][NH:33][C:34]([CH:36]4[CH2:38][CH2:37]4)=[O:35])=[C:30]([F:41])[CH:29]=3)=[O:27])[CH2:24][C:23]3[CH:22]=[N:21][N:20]([CH3:42])[C:19]=3[NH:18][C:17]=2[CH:43]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[C:8]1([CH3:9])[CH:7]=[CH:6][C:5]([S:1]([OH:4])(=[O:2])=[O:3])=[CH:11][CH:10]=1.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]2[N:25]([C:26]([C:28]3[CH:40]=[CH:39][C:31]([CH2:32][NH:33][C:34]([CH:36]4[CH2:37][CH2:38]4)=[O:35])=[C:30]([F:41])[CH:29]=3)=[O:27])[CH2:24][C:23]3[CH:22]=[N:21][N:20]([CH3:42])[C:19]=3[NH:18][C:17]=2[CH:43]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 85570p-ToluenesulfonateHCID 135564707VA-111913

Product 1

HCID 135565015Cyclopropanecarboxamide, N-((4-((8-chloro-4,10-dihydro-1-methylpyrazolo(3,4-b)(1,5)benzodiazepin-5(1H)-yl)carbonyl)-2-fluorophenyl)methyl)-, 4-methylbenzenesulfonate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
22.5 °C

Procedure

The tosylate salt of the present invention may be prepared as follows: A mixture of cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide (prepared by the method described in PCT/DK2005/000540) and para-toluenesulphonic acid are combined in a suitable solvent (e.g. methanol) and stirred at a suitable temperature (e.g. 20 to 25° C.) for a period of time (e.g. 6 to 24 hours). The solvent is then removed (e.g. by rotary evaporation). The dried material may then be suspended in a suitable solvent (e.g. t-butyl methyl ether) and then sonicated for a suitable time (e.g. 2 to 6 hours) at a suitable temperature (e.g. 50 to 70° C.). The solids may then be collected (e.g. by centrifugation) and dried under vacuum to yield cyclopropanecarboxylic acid 4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-2-fluoro-benzylamide para-toluenesulphonate in amorphous form.

Workup

  1. customprepared by the method
  2. customThe solvent is then removed
  3. custom(e.g. by rotary evaporation)
  4. customsonicated for a suitable time (e.g. 2 to 6 hours) at a suitable temperature (e.g. 50 to 70° C.)
  5. customThe solids may then be collected (e.g. by centrifugation)
  6. customdried under vacuum

Sources & evidence

ORD record
ord-a0e6e6ea850f49c58c84ff3804cf4128
Source dataset
uspto-grants-2015_07
Patent number
US09073928B2

Reaction notes

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