1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 86610618, compound

HRID 506381Notes

Reaction equation

HRID 506381 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([C:40](O)=[O:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2].Cl.C([O:50][C:51](=[O:56])[CH2:52][CH2:53][NH:54][CH3:55])(C)(C)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(N(CC)CC)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:37])([F:39])[F:38])[CH:27]=3)[C:22]([C:40](=[O:41])[N:54]([CH2:53][CH2:52][C:51]([OH:56])=[O:50])[CH3:55])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86610553HCID 86610553, compoundHCID 86610619HCID 86610619, compound

Product 1

HCID 86610618HCID 86610618, compoundYield 98.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-carboxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (200 mg) is dissolved in N,N-dimethylformamide (2 ml), and thereto are added triethylamine (53 μl), 3-methylaminopropionic acid tert-butyl ester hydrochloride (101.14 mg), 1-hydroxybenzotriazole hydrate (65 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (92 mg) under ice-cooling. The mixture is stirred at room temperature for 21 hours. The reaction solution is concentrated under reduced pressure, then the residue is partitioned by adding a saturated aqueous sodium bicarbonate solution and ethyl acetate, and the organic layer is concentrated under reduced pressure. The resulting residue is dissolved in a solution (2 ml) of 4N hydrochloric acid in 1,4-dioxane and stirred at room temperature for 1 hour. To the reaction solution is added excessive saturated aqueous sodium bicarbonate solution, and the mixture is neutralized with 1N HCl, then extracted with ethyl acetate and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→19:1) to give (2R,4S)-4-([3,5-bis-(trifluoromethyl)benzyl]-{5-[(2-carboxyethyl)methylcarbamoyl]pyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (223 mg). MS (m/z): 713 [M+H]+.

Workup

  1. temperaturecooling
  2. concentrationThe reaction solution is concentrated under reduced pressure
  3. customthe residue is partitioned
  4. additionby adding a saturated aqueous sodium bicarbonate solution and ethyl acetate
  5. concentrationthe organic layer is concentrated under reduced pressure
  6. dissolutionThe resulting residue is dissolved in a solution (2 ml) of 4N hydrochloric acid in 1,4-dioxane
  7. stirringstirred at room temperature for 1 hour
  8. additionTo the reaction solution is added excessive saturated aqueous sodium bicarbonate solution
  9. extractionextracted with ethyl acetate
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→19:1)

Sources & evidence

ORD record
ord-00e230ad122a4bd58e0ef5c9a220d220
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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