Diisopropylethylamine → 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 N2,N6-bis(tert-butoxycarbonyl)-L-lysyl-L-alaninate

HRID 1968306Notes

Reaction equation

HRID 1968306 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:22]([OH:24])=O)[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.FC(F)(F)C(O)=O.[NH2:64][C@H:65]([C:67]([O:69][CH2:70][CH2:71][O:72][C:73]1[CH:78]=[CH:77][C:76]([C:79]2[C:84]([C:85]#[N:86])=[C:83]([N:87]3[CH2:91][CH2:90][CH2:89][CH2:88]3)[N:82]=[C:81]([S:92][CH2:93][C:94]3[N:95]=[C:96]([C:99]4[CH:104]=[CH:103][C:102]([Cl:105])=[CH:101][CH:100]=4)[S:97][CH:98]=3)[C:80]=2[C:106]#[N:107])=[CH:75][CH:74]=1)=[O:68])[CH3:66]>CN(C=O)C.O.C(#N)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:22]([NH:64][C@H:65]([C:67]([O:69][CH2:70][CH2:71][O:72][C:73]1[CH:78]=[CH:77][C:76]([C:79]2[C:84]([C:85]#[N:86])=[C:83]([N:87]3[CH2:88][CH2:89][CH2:90][CH2:91]3)[N:82]=[C:81]([S:92][CH2:93][C:94]3[N:95]=[C:96]([C:99]4[CH:100]=[CH:101][C:102]([Cl:105])=[CH:103][CH:104]=4)[S:97][CH:98]=3)[C:80]=2[C:106]#[N:107])=[CH:75][CH:74]=1)=[O:68])[CH3:66])=[O:24])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7349648(2S)-2,6-bis((((tert-butoxy)carbonyl)amino))hexanoic acidHCID 687647022-{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-alaninate trifluoroacetate

Product 1

HCID 866438502-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl N2,N6-bis(tert-butoxycarbonyl)-L-lysyl-L-alaninate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

166 mg (0.478 mmol) of N2,N6-bis(tert-butoxycarbonyl)-L-lysine were initially charged in 6.4 ml of DMF. 88 mg (0.652 mmol) of 1-hydroxy-1H-benzotriazole hydrate, 100 mg (0.522 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.379 ml (2.173 mmol) of N,N-diisopropylethylamine were added, 330 mg (0.435 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 L-alaninate trifluoroacetate (Example 40) were then added and the mixture was stirred at RT overnight. Water/acetonitrile was added to the reaction solution in such an amount that a clear solution was formed. This was purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 216 mg (44% of theory) of the target compound.

Workup

  1. customwas formed
  2. customThis was purified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-c58d413322fc4366966248f344e111b4
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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