Hydrochloric Acid → 2-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl 3-amino-L-alanyl-L-alaninate bis(trifluoroacetate)

HRID 1968351Notes

Reaction equation

HRID 1968351 reaction equation
C(OC([NH:8][C@H:9]([C:19]([NH:21][C@H:22]([C:24]([O:26][CH2:27][CH2:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[C:41]([C:42]#[N:43])=[C:40]([N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)[N:39]=[C:38]([S:49][CH2:50][C:51]3[N:52]=[C:53]([C:56]4[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=4)[S:54][CH:55]=3)[C:37]=2[C:63]#[N:64])=[CH:32][CH:31]=1)=[O:25])[CH3:23])=[O:20])[CH2:10][NH:11]C(OC(C)(C)C)=O)=O)(C)(C)C.Cl.[F:66][C:67]([F:72])([F:71])[C:68]([OH:70])=[O:69]>ClCCl.C(OCC)C>[F:66][C:67]([F:72])([F:71])[C:68]([OH:70])=[O:69].[F:66][C:67]([F:72])([F:71])[C:68]([OH:70])=[O:69].[NH2:11][CH2:10][C@@H:9]([C:19]([NH:21][C@H:22]([C:24]([O:26][CH2:27][CH2:28][O:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]2[C:41]([C:42]#[N:43])=[C:40]([N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)[N:39]=[C:38]([S:49][CH2:50][C:51]3[N:52]=[C:53]([C:56]4[CH:57]=[CH:58][C:59]([Cl:62])=[CH:60][CH:61]=4)[S:54][CH:55]=3)[C:37]=2[C:63]#[N:64])=[CH:34][CH:35]=1)=[O:25])[CH3:23])=[O:20])[NH2:8]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid3×HCID 6422Trifluoroacetic acidHCID 866438512-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl N-(tert-butoxycarbonyl)-3-((tert-butoxycarbonyl)amino)-L-alanyl-L-alaninate

Product 1

HCID 866438582-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl 3-amino-L-alanyl-L-alaninate bis(trifluoroacetate)

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 6344DichloromethaneSolvent

Procedure

290 mg (0.311 mmol) of 2-{4-(2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl N-(tert-butoxycarbonyl)-3-((tert-butoxycarbonyl)amino)-L-alanyl-L-alaninate were dissolved in 5 ml dichloromethane, and 3.113 ml of a 1N solution of hydrogen chloride in diethyl ether were added. After 6 hours of stirring, a further 3.113 ml of a 1N solution of hydrogen chloride in diethyl ether were added and the mixture was stirred at room temperature overnight. Another 10 ml of a 1N solution of hydrogen chloride in diethyl ether were added, and stirring at room temperature was continued for a further 24 hours. The precipitated solid was then filtered off with suction, washed with diethyl ether and dried under reduced pressure. The crude product was dissolved in 2 ml of dichloromethane, and 0.126 ml (1.632 mmol) of trifluoroacetic acid was added. After 6 hours of stirring, the reaction mixture was concentrated and the residue was purified by preparative HPLC (acetonitrile/water+0.1% TFA). 81 mg (27% of theory) of the target compound were obtained.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. stirringstirring at room temperature
  3. waitwas continued for a further 24 hours
  4. filtrationThe precipitated solid was then filtered off with suction
  5. washwashed with diethyl ether
  6. customdried under reduced pressure
  7. dissolutionThe crude product was dissolved in 2 ml of dichloromethane
  8. stirringAfter 6 hours of stirring
  9. concentrationthe reaction mixture was concentrated
  10. customthe residue was purified by preparative HPLC (acetonitrile/water+0.1% TFA)
  11. custom81 mg (27% of theory) of the target compound were obtained

Sources & evidence

ORD record
ord-7507bf4b2cbe4f94b11adb209eedfac4
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

Loading…