Diisopropylethylamine → 2-{4-(2-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl N2,N6-bis(tert-butoxycarbonyl)-L-lysyl-L-alaninate

HRID 1968298Notes

Reaction equation

HRID 1968298 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].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.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]([S:87][CH2:88][C:89]3[N:90]=[C:91]([C:94]4[CH:99]=[CH:98][C:97]([Cl:100])=[CH:96][CH:95]=4)[S:92][CH:93]=3)[N:82]=[C:81]([N:101]3[CH2:104][CH2:103][CH2:102]3)[C:80]=2[C:105]#[N:106])=[CH:75][CH:74]=1)=[O:68])[CH3:66]>CN(C=O)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]([S:87][CH2:88][C:89]3[N:90]=[C:91]([C:94]4[CH:95]=[CH:96][C:97]([Cl:100])=[CH:98][CH:99]=4)[S:92][CH:93]=3)[N:82]=[C:81]([N:101]3[CH2:102][CH2:103][CH2:104]3)[C:80]=2[C:105]#[N:106])=[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

7

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 687629082-{4-(2-(azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl L-alaninate trifluoroacetate

Product 1

HCID 866438482-{4-(2-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl N2,N6-bis(tert-butoxycarbonyl)-L-lysyl-L-alaninate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

32.73 mg (0.094 mmol) of N2,N6-bis(tert-butoxycarbonyl)-L-lysine were initially charged in 1.5 ml of DMF. 19.8 mg (0.103 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 17.4 mg (0.129 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 55.5 mg (0.429 mmol) of N,N-diisopropylethylamine were added, and the mixture was then stirred at RT for 15 min, 64 mg (0.086 mmol) of 2-{4-(2-(azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl L-alaninate trifluoroacetate (Example 45) were then added and the mixture was stirred at RT overnight. The crude product was purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 76 mg (92% of theory) of the target compound.

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. customThe crude product was purified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-84571fb7f34743da9b1e605354f2436c
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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