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-alanyl-L-alaninate

HRID 1968299Notes

Reaction equation

HRID 1968299 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])=[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:56]([O:58][CH2:59][CH2:60][O:61][C:62]1[CH:67]=[CH:66][C:65]([C:68]2[C:73]([C:74]#[N:75])=[C:72]([N:76]3[CH2:80][CH2:79][CH2:78][CH2:77]3)[N:71]=[C:70]([S:81][CH2:82][C:83]3[N:84]=[C:85]([C:88]4[CH:93]=[CH:92][C:91]([Cl:94])=[CH:90][CH:89]=4)[S:86][CH:87]=3)[C:69]=2[C:95]#[N:96])=[CH:64][CH:63]=1)=[O:57])[CH3:55]>CN(C=O)C.O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([NH:53][C@H:54]([C:56]([O:58][CH2:59][CH2:60][O:61][C:62]1[CH:67]=[CH:66][C:65]([C:68]2[C:73]([C:74]#[N:75])=[C:72]([N:76]3[CH2:77][CH2:78][CH2:79][CH2:80]3)[N:71]=[C:70]([S:81][CH2:82][C:83]3[N:84]=[C:85]([C:88]4[CH:89]=[CH:90][C:91]([Cl:94])=[CH:92][CH:93]=4)[S:86][CH:87]=3)[C:69]=2[C:95]#[N:96])=[CH:64][CH:63]=1)=[O:57])[CH3:55])=[O:13])[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 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 594356502-{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-alanyl-L-alaninate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

26.756 g (141.406 mmol) of N-(tert-butoxycarbonyl)-L-alanine together with 29.572 g (154.261 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 29.529 g (192.827 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 55.979 ml (321.378 mmol) of N,N-diisopropylethylamine were dissolved in 10 l DMF. 97.60 g (128.551 mmol) of trifluoroacetic acid-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 (1:1) were then added, and the mixture was stirred at room temperature for 3 h. The reaction mixture was stirred into water and extracted with dichloromethane. The organic phase was washed with water, dried over sodium sulfate, filtered and concentrated. The residue was triturated with diethyl ether, and the solid was filtered off with suction and air-dried. This gave 95 g (91% of theory) of the desired target compound.

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic phase was washed with water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was triturated with diethyl ether
  7. filtrationthe solid was filtered off with suction
  8. customair-dried

Sources & evidence

ORD record
ord-5585a0177b574219983de67a47514403
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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