1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 86610620, compound

HRID 506382Notes

Reaction equation

HRID 506382 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:47][C:48](=[O:52])[CH2:49][CH2:50][NH2:51].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:38])([F:39])[F:37])[CH:27]=3)[C:22]([C:40](=[O:41])[NH:51][CH2:50][CH2:49][C:48]([OH:52])=[O:47])=[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 2734767Methyl 3-aminopropanoate hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86610553HCID 86610553, compound

Product 1

HCID 86610620HCID 86610620, compoundYield 85.3%

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-aminopropionic acid methyl ester hydrochloride (67 mg), 1-hydroxybenzotriazole hydrate (65 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (92 mg) under ice-cooling. The mixture is stirred 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 methanol (2 ml), and thereto is added 5N aqueous NaOH solution (1 ml), and the mixture is stirred at room temperature for 2 hours. To the reaction solution is added 6N HCl (0.85 ml), and then the mixture is extracted with ethyl acetate and the organic layer is 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)carbamoyl]pyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (190 mg). MS (m/z): 699 [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 methanol (2 ml)
  7. additionis added 5N aqueous NaOH solution (1 ml)
  8. stirringthe mixture is stirred at room temperature for 2 hours
  9. additionTo the reaction solution is added 6N HCl (0.85 ml)
  10. extractionthe mixture is extracted with ethyl acetate
  11. concentrationthe organic layer is concentrated under reduced pressure
  12. customThe resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→19: 1)

Sources & evidence

ORD record
ord-c9f896bfac11480187230a5ccc6a83dd
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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