2,6-Dimethoxypyridine-3-carboxylic acid → acetic acid (1RS,3RS,4RS)-4-{[1-(2,6-dimethoxy-pyridin-3-yl)methanoyl]amino}-3-(3-ethoxy-4-methoxyphenyl)cyclohexyl ester

HRID 73491Notes

Reaction equation

HRID 73491 reaction equation
[CH3:1][O:2][C:3]1[N:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=O.Cl.C(N=C=NCCCN(C)C)C.[NH2:26][CH:27]1[CH2:32][CH2:31][CH:30]([O:33][C:34](=[O:36])[CH3:35])[CH2:29][CH:28]1[C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[C:39]([O:45][CH2:46][CH3:47])[CH:38]=1>CN(C)C1C=CN=CC=1.ClCCl>[CH3:1][O:2][C:3]1[C:4]([C:5]([NH:26][CH:27]2[CH2:32][CH2:31][CH:30]([O:33][C:34](=[O:36])[CH3:35])[CH2:29][CH:28]2[C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[C:39]([O:45][CH2:46][CH3:47])[CH:38]=2)=[O:7])=[CH:8][CH:9]=[C:10]([O:12][CH3:13])[N:11]=1

Participants

6

Reactant 3

HCID 8531782,6-Dimethoxypyridine-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67022406acetic acid (1RS,3RS,4RS)-4-amino-3-(3-ethoxy-4-methoxyphenyl)cyclohexyl ester2×

Product 1

HCID 67022608acetic acid (1RS,3RS,4RS)-4-{[1-(2,6-dimethoxy-pyridin-3-yl)methanoyl]amino}-3-(3-ethoxy-4-methoxyphenyl)cyclohexyl esterYield 102.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

555 mg of 2,6-dimethoxynicotinic acid and 581 mg of N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride are placed in a flask under nitrogen. 778 mg of acetic acid (1RS,3RS,4RS)-4-amino-3-(3-ethoxy-4-methoxyphenyl)cyclohexyl ester (compound B1) and 2 mg of 4-dimethylaminopyridine both as solution in dichloromethane are added and the solution stirred for 1 h at 40° C., than 42 h at room temperature. The reaction is quenched with 5 ml of water. After phase separation the organic layer is washed with 2.5 ml of saturated potassium hydrogencarbonate solution. After drying the organic layer with magnesium sulfate the solvent is removed to give 1.227 g of the crude title compound which are used for the following step without further purification.

Workup

  1. customThe reaction is quenched with 5 ml of water
  2. customAfter phase separation the organic layer
  3. washis washed with 2.5 ml of saturated potassium hydrogencarbonate solution
  4. dry with materialAfter drying the organic layer with magnesium sulfate the solvent
  5. customis removed

Sources & evidence

ORD record
ord-a9afeb771a8c41d790135688a86a45c2
Source dataset
uspto-grants-2014_09
Patent number
US08829189B2

Reaction notes

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