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 1-(tert-butoxycarbonyl)-L-prolyl-L-alaninate

HRID 1968307Notes

Reaction equation

HRID 1968307 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=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.[NH2:55][C@H:56]([C:58]([O:60][CH2:61][CH2:62][O:63][C:64]1[CH:69]=[CH:68][C:67]([C:70]2[C:75]([C:76]#[N:77])=[C:74]([N:78]3[CH2:82][CH2:81][CH2:80][CH2:79]3)[N:73]=[C:72]([S:83][CH2:84][C:85]3[N:86]=[C:87]([C:90]4[CH:95]=[CH:94][C:93]([Cl:96])=[CH:92][CH:91]=4)[S:88][CH:89]=3)[C:71]=2[C:97]#[N:98])=[CH:66][CH:65]=1)=[O:59])[CH3:57]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([NH:55][C@H:56]([C:58]([O:60][CH2:61][CH2:62][O:63][C:64]1[CH:69]=[CH:68][C:67]([C:70]2[C:75]([C:76]#[N:77])=[C:74]([N:78]3[CH2:79][CH2:80][CH2:81][CH2:82]3)[N:73]=[C:72]([S:83][CH2:84][C:85]3[N:86]=[C:87]([C:90]4[CH:91]=[CH:92][C:93]([Cl:96])=[CH:94][CH:95]=4)[S:88][CH:89]=3)[C:71]=2[C:97]#[N:98])=[CH:66][CH:65]=1)=[O:59])[CH3:57])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 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 687628552-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl)phenoxy}ethyl 1-(tert-butoxycarbonyl)-L-prolyl-L-alaninate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

202 mg (0.942 mmol) of 1-(tert-butoxycarbonyl)-L-proline together with 246 mg (1.284 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 157 mg (1.027 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 0.746 ml (4.281 mmol) of N,N-diisopropylethylamine were dissolved in 7.5 ml of DMF, after which 650 mg (0.856 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-alaninate trifluoroacetate were added. After stirring at room temperature overnight, the reaction mixture was purified by preparative HPLC (acetonitrile/water). This gave 495 mg (69% of theory) of the target compound.

Workup

  1. customthe reaction mixture was purified by preparative HPLC (acetonitrile/water)

Sources & evidence

ORD record
ord-3af07387b6e8496a8da4b162fba16aa0
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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