N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → 2-{4-(2-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl N-(tert-butoxycarbonyl)-beta-alaninate

HRID 1621312Notes

Reaction equation

HRID 1621312 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN(C)CCCN=[C:21]=[N:22][CH2:23][CH3:24].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[S:34][CH:35]=[C:36]([CH2:38][S:39][C:40]3[C:45]([C:46]#[N:47])=[C:44]([C:48]4[CH:53]=[CH:52][C:51]([O:54][CH2:55][CH2:56]O)=[CH:50][CH:49]=4)[C:43]([C:58]#[N:59])=[CH:42][N:41]=3)[N:37]=2)=[CH:29][CH:28]=1>CN(C=O)C.ClCCl.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([O:13][CH2:56][CH2:55][O:54][C:51]1[CH:52]=[CH:53][C:48]([C:44]2[C:45]([C:46]#[N:47])=[C:40]([S:39][CH2:38][C:36]3[N:37]=[C:33]([C:30]4[CH:29]=[CH:28][C:27]([Cl:26])=[CH:32][CH:31]=4)[S:34][CH:35]=3)[N:41]=[C:42]([N:22]3[CH2:21][CH2:24][CH2:23]3)[C:43]=2[C:58]#[N:59])=[CH:49][CH:50]=1)=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86698909{(2-(4-Chlorophenyl)-1,3-thiazol-4-ylmethyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

Product 1

HCID 687657592-{4-(2-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl N-(tert-butoxycarbonyl)-beta-alaninate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

101 mg (0.536 mmol) of N-(tert-butoxycarbonyl)-beta-alanine were initially charged in 2 ml of DMF/dichloromethane (1:1). 44.5 mg (0.232 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 10.9 mg (0.89 mmol) of 4-dimethylaminopyridine and 100 mg (0.179 mmol) of 2-(azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-ylmethyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 8) were added, and the mixture was then stirred at RT overnight. The crude product was purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 118 mg (90% of theory) of the target compound.

Workup

  1. customThe crude product was purified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-8a4a7a93f04547a584ec7a585cc35cec
Source dataset
uspto-grants-2014_07
Patent number
US08772498B2

Reaction notes

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