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 N-(tert-butoxycarbonyl)-L-leucinate

HRID 1968312Notes

Reaction equation

HRID 1968312 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])=[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.[Cl:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]2[S:57][CH:58]=[C:59]([CH2:61][S:62][C:63]3[C:68]([C:69]#[N:70])=[C:67]([C:71]4[CH:76]=[CH:75][C:74]([O:77][CH2:78][CH2:79]O)=[CH:73][CH:72]=4)[C:66]([C:81]#[N:82])=[C:65]([N:83]4[CH2:87][CH2:86][CH2:85][CH2:84]4)[N:64]=3)[N:60]=2)=[CH:52][CH:51]=1>CN(C=O)C.O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([O:16][CH2:79][CH2:78][O:77][C:74]1[CH:73]=[CH:72][C:71]([C:67]2[C:66]([C:81]#[N:82])=[C:65]([N:83]3[CH2:84][CH2:85][CH2:86][CH2:87]3)[N:64]=[C:63]([S:62][CH2:61][C:59]3[N:60]=[C:56]([C:53]4[CH:52]=[CH:51][C:50]([Cl:49])=[CH:55][CH:54]=4)[S:57][CH:58]=3)[C:68]=2[C:69]#[N:70])=[CH:76][CH:75]=1)=[O:15])[CH2:10][CH:11]([CH3:12])[CH3:13])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 46847262Neladenoson

Product 1

HCID 687646672-{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)-L-leucinate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

0.89 g (3.82 mmol) of N-(tert-butoxycarbonyl)-L-leucine were initially charged in 10 ml of DMF, and 0.81 g (4.18 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.80 g (5.23 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 1.13 g (8.71 mmol) of N,N-diisopropylethylamine were added. The mixture was stirred until a clear solution had been obtained. 1.00 g (1.74 mmol) of 2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)-6-(pyrrolidin-1-yl)pyridine-3,5-dicarbonitrile was then added, and the mixture was stirred at room temperature for 18 h. The mixture was added to 300 ml of water. The residue formed was filtered off with suction and washed with 50 ml of water. The crude product was dissolved in 50 ml of dichloromethane. The aqueous phase was separated off and the organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure gave 1.37 g (100% of theory) of the desired target compound.

Workup

  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 50 ml of water
  6. dissolutionThe crude product was dissolved in 50 ml of dichloromethane
  7. customThe aqueous phase was separated off
  8. dry with materialthe organic phase was dried over sodium sulfate
  9. customRemoval of the solvent under reduced pressure
  10. customgave 1.37 g (100% of theory) of the desired target compound

Sources & evidence

ORD record
ord-be1371cb60e3413c8663e9ad7d48dd0d
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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