Azetidine → 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 1621313Notes

Reaction equation

HRID 1621313 reaction equation
[NH:1]1[CH2:4][CH2:3][CH2:2]1.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:13][CH:14]=[C:15]([CH2:17][S:18][C:19]3[C:24]([C:25]#[N:26])=[C:23]([C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][OH:36])=[CH:29][CH:28]=4)[C:22]([C:37]#[N:38])=[CH:21][N:20]=3)[N:16]=2)=[CH:8][CH:7]=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].Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.CN(C=O)C.O.C1COCC1.ClCCl>[C:39]([O:43][C:44]([NH:46][C@H:47]([C:59]([O:36][CH2:35][CH2:34][O:33][C:30]1[CH:31]=[CH:32][C:27]([C:23]2[C:24]([C:25]#[N:26])=[C:19]([S:18][CH2:17][C:15]3[N:16]=[C:12]([C:9]4[CH:8]=[CH:7][C:6]([Cl:5])=[CH:11][CH:10]=4)[S:13][CH:14]=3)[N:20]=[C:21]([N:1]3[CH2:4][CH2:3][CH2:2]3)[C:22]=2[C:37]#[N:38])=[CH:28][CH:29]=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

9

Reactant 4

HCID 10422AzetidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7015803Boc-orn(boc)-OHHCID 86698909{(2-(4-Chlorophenyl)-1,3-thiazol-4-ylmethyl}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 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
40 °C

Procedure

75 mg (0.134 mmol) of 2-(azetidin-1-O-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-ylmethyl}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-2cb4a0f9b6824ad8b7bb19eb4483ecb2
Source dataset
uspto-grants-2014_07
Patent number
US08772498B2

Reaction notes

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