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 1968300Notes

Reaction equation

HRID 1968300 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=NCC.[N:26]1([C:30]2[C:35]([C:36]#[N:37])=[C:34]([C:38]3[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH2:46]O)=[CH:40][CH:39]=3)[C:33]([C:48]#[N:49])=[C:32]([S:50][CH2:51][C:52]3[N:53]=[C:54]([C:57]4[CH:62]=[CH:61][C:60]([Cl:63])=[CH:59][CH:58]=4)[S:55][CH:56]=3)[N:31]=2)[CH2:29][CH2:28][CH2:27]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][CH2:46][CH2:45][O:44][C:41]1[CH:42]=[CH:43][C:38]([C:34]2[C:33]([C:48]#[N:49])=[C:32]([S:50][CH2:51][C:52]3[N:53]=[C:54]([C:57]4[CH:62]=[CH:61][C:60]([Cl:63])=[CH:59][CH:58]=4)[S:55][CH:56]=3)[N:31]=[C:30]([N:26]3[CH2:27][CH2:28][CH2:29]3)[C:35]=2[C:36]#[N:37])=[CH:39][CH:40]=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 468530232-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}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-yl)methyl}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-20bbbf48733e4ea1b78940fe7e22cefe
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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