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 L-isoleucyl-L-alaninate hydrochloride

HRID 1621343Notes

Reaction equation

HRID 1621343 reaction equation
C(OC([NH:8][C@H:9]([C:14]([NH:16][C@H:17]([C:19]([O:21][CH2:22][CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[C:36]([C:37]#[N:38])=[C:35]([N:39]3[CH2:43][CH2:42][CH2:41][CH2:40]3)[N:34]=[C:33]([S:44][CH2:45][C:46]3[N:47]=[C:48]([C:51]4[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=4)[S:49][CH:50]=3)[C:32]=2[C:58]#[N:59])=[CH:27][CH:26]=1)=[O:20])[CH3:18])=[O:15])[C@H:10]([CH2:12][CH3:13])[CH3:11])=O)(C)(C)C.Cl>ClCCl.C(OCC)C>[ClH:57].[NH2:8][C@H:9]([C:14]([NH:16][C@H:17]([C:19]([O:21][CH2:22][CH2:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]2[C:36]([C:37]#[N:38])=[C:35]([N:39]3[CH2:40][CH2:41][CH2:42][CH2:43]3)[N:34]=[C:33]([S:44][CH2:45][C:46]3[N:47]=[C:48]([C:51]4[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=4)[S:49][CH:50]=3)[C:32]=2[C:58]#[N:59])=[CH:29][CH:30]=1)=[O:20])[CH3:18])=[O:15])[C@H:10]([CH2:12][CH3:13])[CH3:11]

Participants

5

Reactant 2

HCID 313Hydrochloric Acid2×HCID 687635572-{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)-L-isoleucyl-L-alaninate

Product 1

HCID 687639812-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl L-isoleucyl-L-alaninate hydrochloride

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Procedure

414 mg (0.482 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)-L-isoleucyl-L-alaninate were dissolved in 3 ml dichloromethane, and 4.822 ml of a 1N solution of hydrogen chloride in diethyl ether were added. After 6 hours of stirring, 2 ml of a 1N solution of hydrogen chloride in diethyl ether were added, and the mixture was stirred at room temperature for a further 24 hours. The precipitated solid was filtered off with suction, washed with diethyl ether and dried under reduced pressure. Since the reaction was still incomplete, the solid was stirred in 5 ml of a 1N solution of hydrogen chloride in diethyl ether for a further 24 h. The precipitated solid was filtered off with suction, washed with diethyl ether and dried under reduced pressure. 312 mg (81% of theory) of the target compound were obtained.

Workup

  1. stirringthe mixture was stirred at room temperature for a further 24 hours
  2. filtrationThe precipitated solid was filtered off with suction
  3. washwashed with diethyl ether
  4. customdried under reduced pressure
  5. stirringthe solid was stirred in 5 ml of a 1N solution of hydrogen chloride in diethyl ether for a further 24 h
  6. filtrationThe precipitated solid was filtered off with suction
  7. washwashed with diethyl ether
  8. customdried under reduced pressure
  9. custom312 mg (81% of theory) of the target compound were obtained

Sources & evidence

ORD record
ord-e66cd05fd5de44c58020f0b1cc383d8b
Source dataset
uspto-grants-2014_07
Patent number
US08772498B2

Reaction notes

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