1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → methyl 2-[1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxyphenyl acetyl]-2-pyrrolidinylmethoxy]pyridine-5-carboxylate

HRID 350407Notes

Reaction equation

HRID 350407 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][N:9]=1.[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][C:26](=[O:40])[NH:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][C:35](O)=[O:36])=[CH:30][C:29]=1[O:38][CH3:39].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][C:26](=[O:40])[NH:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][C:35]([N:1]2[CH2:5][CH2:4][CH2:3][CH:2]2[CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][N:9]=2)=[O:36])=[CH:30][C:29]=1[O:38][CH3:39]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23511785Methyl 2-(2-pyrrolidinyl)methoxypyridine-5-carboxylateHCID 235118674-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid

Product 1

HCID 23512353methyl 2-[1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxyphenyl acetyl]-2-pyrrolidinylmethoxy]pyridine-5-carboxylateYield 69.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of methyl 2-(2-pyrrolidinyl)methoxypyridine-5-carboxylate (370 mg, 1.57 mmol), 4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid (525 mg, 1.57 mmol), 4-DMAP (230 mg, 1.88 mmol) in DMF (10 ml) was added EDC.HCl (360 mg, 1.88 mmol) at room temperature. The resulting mixture was stirred at room temperature for 20 hr. The mixture was pored into ice-water. The solid was collected, washed with water and air-dried. The crude solid was purified by silica-gel (30 ml) column chromatography with CHCl3-EtOH (98:2, v/v) as eluent and crystallized with Et2O to give methyl 2-[1-[4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenyl acetyl]-2-pyrrolidinylmethoxy]pyridine-5-carboxylate (600 mg, 69%) as an amorphous solid. 1H-NMR (CDCl3) δ 0.21 and 2.01 (each m, 4 H), 3.45–4.50 (series of s and m, 13 H which contains amide-isomers), 6.58–8.83 (series of s and m, 12 H which contains amide-isomers)

Workup

  1. customThe solid was collected
  2. washwashed with water
  3. customair-dried
  4. customThe crude solid was purified by silica-gel (30 ml) column chromatography with CHCl3-EtOH (98:2
  5. customv/v) as eluent and crystallized with Et2O

Sources & evidence

ORD record
ord-b98e29df47704c25bca5007838abf7df
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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