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 1968315Notes

Reaction equation

HRID 1968315 reaction equation
[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]

Participants

8

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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.

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 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

Sources & evidence

ORD record
ord-e529eaeb2e364364b72a65c6de8d0a71
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

Loading…