Dichloromethane → 2-{4-(2-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl N2,N5-bis(tert-butoxycarbonyl)-L-ornithinate

HRID 1968301Notes

Reaction equation

HRID 1968301 reaction equation
[N:1]1([C:5]2[C:10]([C:11]#[N:12])=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][OH:22])=[CH:15][CH:14]=3)[C:8]([C:23]#[N:24])=[C:7]([S:25][CH2:26][C:27]3[N:28]=[C:29]([C:32]4[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=4)[S:30][CH:31]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[C:39]([O:43][C:44]([NH:46][C@H:47]([C:59](O)=[O:60])[CH2:48][CH2:49][CH2:50][NH:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])=[O:45])([CH3:42])([CH3:41])[CH3:40].ClCCl.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.CN(C=O)C.O.C1COCC1>[C:39]([O:43][C:44]([NH:46][C@H:47]([C:59]([O:22][CH2:21][CH2:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([C:9]2[C:8]([C:23]#[N:24])=[C:7]([S:25][CH2:26][C:27]3[N:28]=[C:29]([C:32]4[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=4)[S:30][CH:31]=3)[N:6]=[C:5]([N:1]3[CH2:2][CH2:3][CH2:4]3)[C:10]=2[C:11]#[N:12])=[CH:14][CH:15]=1)=[O:60])[CH2:48][CH2:49][CH2:50][NH:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])=[O:45])([CH3:41])([CH3:40])[CH3:42]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7015803Boc-orn(boc)-OHHCID 468530232-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

Product 1

HCID 708661402-{4-(2-(Azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyanopyridin-4-yl)phenoxy}ethyl N2,N5-bis(tert-butoxycarbonyl)-L-ornithinate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
40 °C

Procedure

75 mg (0.134 mmol) of 2-(azetidin-1-yl)-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 8), 133.53 mg (0.402 mmol) of N2,N5-bis(tert-butoxycarbonyl)-L-ornithine and 8.18 mg (0.067 mmol) of 4-dimethylaminopyridine were initially charged in 1 ml of DMF. 1 ml of dichloromethane and 33.37 mg (0.174 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added, and the reaction solution was then stirred at 40° C. overnight. After cooling, water/THF was added to the reaction solution in such an amount that a clear solution was formed, and the product was purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 104 mg (89% of theory) of the target compound.

Workup

  1. temperatureAfter cooling
  2. customwas formed
  3. customthe product was purified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-c7bbd47b73bd4561a667d18e4c70b911
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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