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N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → 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 N-(tert-butoxycarbonyl)-beta-alanyl-L-leucinate

HRID 1968315
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1968315
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=O)=[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.[NH2:53][C@H:54]([C:59]([O:61][CH2:62][CH2:63][O:64][C:65]1[CH:70]=[CH:69][C:68]([C:71]2[C:76]([C:77]#[N:78])=[C:75]([N:79]3[CH2:83][CH2:82][CH2:81][CH2:80]3)[N:74]=[C:73]([S:84][CH2:85][C:86]3[N:87]=[C:88]([C:91]4[CH:96]=[CH:95][C:94]([Cl:97])=[CH:93][CH:92]=4)[S:89][CH:90]=3)[C:72]=2[C:98]#[N:99])=[CH:67][CH:66]=1)=[O:60])[CH2:55][CH:56]([CH3:58])[CH3:57]>CN(C=O)C.O>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([NH:53][C@H:54]([C:59]([O:61][CH2:62][CH2:63][O:64][C:65]1[CH:66]=[CH:67][C:68]([C:71]2[C:76]([C:77]#[N:78])=[C:75]([N:79]3[CH2:83][CH2:82][CH2:81][CH2:80]3)[N:74]=[C:73]([S:84][CH2:85][C:86]3[N:87]=[C:88]([C:91]4[CH:96]=[CH:95][C:94]([Cl:97])=[CH:93][CH:92]=4)[S:89][CH:90]=3)[C:72]=2[C:98]#[N:99])=[CH:69][CH:70]=1)=[O:60])[CH2:55][CH:56]([CH3:57])[CH3:58])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 866438522-{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-leucinate trifluoroacetate

Produkt 1

HCID 687647662-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl N-(tert-butoxycarbonyl)-beta-alanyl-L-leucinate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

86 mg (0.45 mmol) of N-(tert-butoxycarbonyl)-beta-alanine were initially charged in 5.0 ml of DMF, and 95 mg (0.49 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 95 mg (0.62 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 266.13 g (2.06 mmol) of N,N-diisopropylethylamine were added. The mixture was stirred until a clear solution had been obtained. 330 mg (0.41 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-leucinate trifluoroacetate were then added, and the mixture was stirred at room temperature for 18 h. The reaction mixture was added to 300 ml of water. The residue formed was filtered off with suction and washed with 20 ml of water. The crude product was suspended in 15 ml of methanol and sonicated in an ultrasonic bath for 5 min. The residue was filtered off with suction and washed with 10 ml of diethyl ether. This gave 0.13 g (37% of theory) of the desired target compound.

Aufarbeitung

  1. customhad been obtained
  2. stirringthe mixture was stirred at room temperature for 18 h
  3. customThe residue formed
  4. filtrationwas filtered off with suction
  5. washwashed with 20 ml of water
  6. customsonicated in an ultrasonic bath for 5 min
  7. filtrationThe residue was filtered off with suction
  8. washwashed with 10 ml of diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-e529eaeb2e364364b72a65c6de8d0a71
Quelldatensatz
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08420825B2

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