Hydrochloric Acid → 1-(5-Chloro-2-methoxy-4-{2-[(S)-1-(4-piperazin-1-yl-phenyl)-ethylamino]-ethyl}-phenyl)-3-(5-cyano-pyrazin-2-yl)-urea dihydrochloride

HRID 1019778Notes

Reaction equation

HRID 1019778 reaction equation
[ClH:1].C(OC([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C@@H:21]([N:23](C(OC(C)(C)C)=O)[CH2:24][CH2:25][C:26]3[CH:31]=[C:30]([O:32][CH3:33])[C:29]([NH:34][C:35]([NH:37][C:38]4[CH:43]=[N:42][C:41]([C:44]#[N:45])=[CH:40][N:39]=4)=[O:36])=[CH:28][C:27]=3[Cl:46])[CH3:22])=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)=O)(C)(C)C.C(OCC)C>CCOC(C)=O>[ClH:46].[ClH:1].[Cl:46][C:27]1[C:26]([CH2:25][CH2:24][NH:23][C@H:21]([C:18]2[CH:19]=[CH:20][C:15]([N:12]3[CH2:13][CH2:14][NH:9][CH2:10][CH2:11]3)=[CH:16][CH:17]=2)[CH3:22])=[CH:31][C:30]([O:32][CH3:33])=[C:29]([NH:34][C:35]([NH:37][C:38]2[CH:43]=[N:42][C:41]([C:44]#[N:45])=[CH:40][N:39]=2)=[O:36])[CH:28]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 674691764-(4-{(S)-1-[tert-Butoxycarbonyl-(2-{2-chloro-4-[3-(5-cyano-pyrazin-2-yl)-ureido]-5-methoxy-phenyl}-ethyl)-amino]-ethyl}-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866781561-(5-Chloro-2-methoxy-4-{2-[(S)-1-(4-piperazin-1-yl-phenyl)-ethylamino]-ethyl}-phenyl)-3-(5-cyano-pyrazin-2-yl)-urea dihydrochlorideYield 34%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A 4N HCl solution in EtOAc (18 mL) was added slowly to a stirred solution of 4-(4-{(S)-1-[tert-butoxycarbonyl-(2-{2-chloro-4-[3-(5-cyano-pyrazin-2-yl)-ureido]-5-methoxy-phenyl}-ethyl)-amino]ethyl}-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (0.1 g) in EtOAc (100 mL) at 0° C. The mixture was allowed to warm to room temperature and stirred for 8 hours. Diethyl ether (50 mL) was added and stirring continued for 15 minutes. The supernatant was decanted and the isolated solid triturated again with diethyl ether (50 mL). The solid was dried under reduced pressure then dissolved in methanol and precipitated back out of solution using diethyl ether. The isolated solid was further triturated with diethyl ether then dried under reduced pressure. The obtained solid was triturated with ethyl acetate, acetone, ethanol followed by diethyl ether and dried at reduced pressure to give the title compound (0.025 g, 34%) as a white solid.

Workup

  1. stirringstirring
  2. waitcontinued for 15 minutes
  3. customThe supernatant was decanted
  4. customthe isolated solid triturated again with diethyl ether (50 mL)
  5. customThe solid was dried under reduced pressure
  6. dissolutionthen dissolved in methanol
  7. customprecipitated back out of solution
  8. customThe isolated solid was further triturated with diethyl ether
  9. customthen dried under reduced pressure
  10. customThe obtained solid was triturated with ethyl acetate, acetone, ethanol
  11. customdried at reduced pressure

Sources & evidence

ORD record
ord-2142f812852f4286b8b5061c8a899d92
Source dataset
uspto-grants-2014_05
Patent number
US08716287B2

Reaction notes

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