Dichloromethane → 2-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(propylamino)pyridin-4-yl)phenoxy}ethyl N-(tert-butoxycarbonyl)-L-alaninate

HRID 1968303Notes

Reaction equation

HRID 1968303 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([CH2:13][S:14][C:15]3[C:20]([C:21]#[N:22])=[C:19]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][OH:32])=[CH:25][CH:24]=4)[C:18]([C:33]#[N:34])=[C:17]([NH:35][CH2:36][CH2:37][CH3:38])[N:16]=3)[N:12]=2)=[CH:4][CH:3]=1.[C:39]([O:43][C:44]([NH:46][C@H:47]([C:49](O)=[O:50])[CH3:48])=[O:45])([CH3:42])([CH3:41])[CH3:40].Cl.CN(C)CCCN=C=NCC.ClCCl>CN(C)C1C=CN=CC=1.CN(C=O)C.ClCCl>[C:39]([O:43][C:44]([NH:46][C@H:47]([C:49]([O:32][CH2:31][CH2:30][O:29][C:26]1[CH:27]=[CH:28][C:23]([C:19]2[C:18]([C:33]#[N:34])=[C:17]([NH:35][CH2:36][CH2:37][CH3:38])[N:16]=[C:15]([S:14][CH2:13][C:11]3[N:12]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[S:9][CH:10]=3)[C:20]=2[C:21]#[N:22])=[CH:24][CH:25]=1)=[O:50])[CH3:48])=[O:45])([CH3:41])([CH3:42])[CH3:40]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 85082Tert-butoxycarbonylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68764668HCID 68764668, compound

Product 1

HCID 687654192-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(propylamino)pyridin-4-yl)phenoxy}ethyl N-(tert-butoxycarbonyl)-L-alaninate

Reagents, catalysts & solvents 2

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

Procedure

758 mg (1.348 mmol) of 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)-6-(propylamino)pyridine-3,5-dicarbonitrile (Example 12), 765 mg (4.043 mmol) of N-(tert-butoxycarbonyl)-L-alanine and 82 mg (0.674 mmol) of 4-dimethylaminopyridine were initially charged in 10.3 ml of DMF/dichloromethane (1:1). 336 mg (1.752 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added, and the reaction solution was then stirred at RT overnight. The reaction solution was freed from dichloromethane and the residue was purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 929 mg (94% of theory) of the target compound.

Workup

  1. customthe residue was purified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-a40c438178a143ca96f20810a268ab64
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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