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)-3-((tert-butoxycarbonyl)amino)-L-alanyl-L-alaninate

HRID 1968310Notes

Reaction equation

HRID 1968310 reaction equation
C1(N[CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)CCCCC1.[C:14]([O:18][C:19]([NH:21][C@H:22]([C:32]([OH:34])=O)[CH2:23][NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:20])([CH3:17])([CH3:16])[CH3:15].[ClH:35].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.[NH2:74][C@H:75]([C:77]([O:79][CH2:80][CH2:81][O:82][C:83]1[CH:88]=[CH:87][C:86]([C:89]2[C:94]([C:95]#[N:96])=[C:93]([N:97]3[CH2:101][CH2:100][CH2:99][CH2:98]3)[N:92]=[C:91]([S:102][CH2:103][C:104]3[N:105]=[C:106](C4C=CC(Cl)=CC=4)[S:107][CH:108]=3)[C:90]=2[C:116]#[N:117])=[CH:85][CH:84]=1)=[O:78])[CH3:76]>CN(C=O)C>[C:14]([O:18][C:19]([NH:21][C@H:22]([C:32]([NH:74][C@H:75]([C:77]([O:79][CH2:80][CH2:81][O:82][C:83]1[CH:88]=[CH:87][C:86]([C:89]2[C:94]([C:95]#[N:96])=[C:93]([N:97]3[CH2:98][CH2:99][CH2:100][CH2:101]3)[N:92]=[C:91]([S:102][CH2:103][C:104]3[N:105]=[C:106]([C:8]4[CH:9]=[CH:10][C:11]([Cl:35])=[CH:12][CH:13]=4)[S:107][CH:108]=3)[C:90]=2[C:116]#[N:117])=[CH:85][CH:84]=1)=[O:78])[CH3:76])=[O:34])[CH2:23][NH:24][C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])=[O:20])([CH3:15])([CH3:16])[CH3:17]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 16218628Boc-Dap(Boc)-OH.DCHAHCID 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 866438512-{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)-3-((tert-butoxycarbonyl)amino)-L-alanyl-L-alaninate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

351 mg (0.724 mmol) of N-(tert-butoxycarbonyl)-3-((tert-butoxycarbonyl)amino)-L-alanine N,N-dicyclohexylamine salt together with 151 mg (0.790 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 151 mg (0.988 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 0.574 ml (3.293 mmol) of N,N-diisopropylethylamine were dissolved in 10 ml of DMF, after which 500 mg (0.659 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. The reaction mixture was stirred at room temperature overnight and then purified twice by preparative HPLC (acetonitrile/water). This gave 290 mg (47% of theory) of the target compound.

Workup

  1. custompurified twice by preparative HPLC (acetonitrile/water)

Sources & evidence

ORD record
ord-a3165e2028074122862d71c1cb3a61cc
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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