1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Tert-Butyl(3R,4S)-3-{[[3-{[(1R,2R)-2-({[(5R)-5,6-bis(nitrooxy)hexyl]oxy}-carbonyl)cyclopropyl]methoxy}-5-(3-methoxypropyl)benzyl](cyclopropyl)amino]-carbonyl}-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate

HRID 1798467Notes

Reaction equation

HRID 1798467 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][O:23][C:24]3[C:29]([Cl:30])=[CH:28][C:27]([CH3:31])=[CH:26][C:25]=3[Cl:32])=[CH:16][CH:15]=2)[C@@H:10]([C:33]([N:35]([CH2:39][C:40]2[CH:41]=[C:42]([CH:51]=[C:52]([CH2:54][CH2:55][CH2:56][O:57][CH3:58])[CH:53]=2)[O:43][CH2:44][C@@H:45]2[CH2:47][C@H:46]2[C:48]([OH:50])=[O:49])[CH:36]2[CH2:38][CH2:37]2)=[O:34])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+:59]([O-:73])([O:61][CH2:62][C@H:63]([O:69][N+:70]([O-:72])=[O:71])[CH2:64][CH2:65][CH2:66][CH2:67]O)=[O:60].Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C)C1C=CN=CC=1>[N+:70]([O:69][C@@H:63]([CH2:62][O:61][N+:59]([O-:73])=[O:60])[CH2:64][CH2:65][CH2:66][CH2:67][O:49][C:48]([C@@H:46]1[CH2:47][C@H:45]1[CH2:44][O:43][C:42]1[CH:41]=[C:40]([CH:53]=[C:52]([CH2:54][CH2:55][CH2:56][O:57][CH3:58])[CH:51]=1)[CH2:39][N:35]([CH:36]1[CH2:37][CH2:38]1)[C:33]([C@@H:10]1[C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][O:23][C:24]3[C:29]([Cl:30])=[CH:28][C:27]([CH3:31])=[CH:26][C:25]=3[Cl:32])=[CH:16][CH:15]=2)[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:9]1)=[O:34])=[O:50])([O-:72])=[O:71]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59556786(2R)-6-hydroxyhexane-1,2-diyl dinitrateHCID 68488708(1R,2R)-2-{[3-{[[((3R,4S)-1-(tert-Butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)amino]methyl}-5-(3-methoxypropyl)phenoxy]methyl}cyclopropanecarboxylic Acid

Product 1

HCID 86641742Tert-Butyl(3R,4S)-3-{[[3-{[(1R,2R)-2-({[(5R)-5,6-bis(nitrooxy)hexyl]oxy}-carbonyl)cyclopropyl]methoxy}-5-(3-methoxypropyl)benzyl](cyclopropyl)amino]-carbonyl}-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R,2R)-2-{[3-{[[((3R,4S)-1-(tert-butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)-amino]methyl}-5-(3-methoxypropyl)phenoxy]methyl}cyclopropanecarboxylic acid (1 eq.) from Example 4/Step 1 in DCM (0.17 M) was added (2R)-6-hydroxyhexane-1,2-diyl dinitrate (1.5 eq., prepared according to the procedure described in WO2005070868/Example 2, incorporated by reference), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.5 eq.), and 4-dimethylaminopyridine (1.5 eq.). The reaction was stirred at rt for 18 h and then concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 40% EtOAc in Hex) to afford the title compound as an oil.

Workup

  1. customprepared
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by flash column chromatography (SiO2, 40% EtOAc in Hex)

Sources & evidence

ORD record
ord-77e302983a4043a39ebce469e54966e6
Source dataset
uspto-grants-2013_01
Patent number
US08343968B2

Reaction notes

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