Diisopropylethylamine → N-[1-(2,3-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-3-[5-(4-methoxyphenyl)pyrimidin-2-yl]propionamide Hydrochloride Salt

HRID 1276363Notes

Reaction equation

HRID 1276363 reaction equation
[ClH:1].C[N:3]([CH3:12])[CH2:4][CH2:5][CH2:6][N:7]=[C:8]=[N:9][CH2:10]C.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=CN=C(CCC(O)=O)N=2)=[CH:17][CH:16]=1.[NH2:32][CH2:33][CH:34]1[CH2:38][CH2:37][N:36]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[C:41]=2[Cl:47])[CH2:35]1.[OH2:48].O[N:50]1[C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=2N=N1.C(N(C(C)C)CC)(C)C>C(Cl)(Cl)Cl.C(OCC)(=O)C>[Cl:47][C:41]1[C:42]([Cl:46])=[CH:43][CH:44]=[CH:45][C:40]=1[CH2:39][N:36]1[CH2:37][CH2:38][CH:34]([CH2:33][NH:32][C:58](=[O:48])[CH2:53][CH2:54][C:8]2[N:7]=[CH:6][C:5]([C:4]3[CH:19]=[CH:20][C:15]([O:14][CH3:13])=[CH:16][CH:17]=3)=[CH:10][N:9]=2)[CH2:35]1.[ClH:1].[Cl:47][C:41]1[C:42]([Cl:46])=[CH:43][CH:44]=[CH:45][C:40]=1[CH2:39][N:36]1[CH2:37][CH2:38][CH:34]([CH2:33][NH:32][C:57](=[O:48])[CH2:56][CH2:55][C:54]2[N:50]=[CH:26][C:21]([C:18]3[CH:17]=[CH:16][C:15]([O:14][CH3:13])=[CH:20][CH:19]=3)=[CH:12][N:3]=2)[CH2:35]1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 114368453-(RS)-aminomethyl-1-(2,3-dichlorobenzyl)-pyrrolidineHCID 185455503-[4-(4-Methoxyphenyl)pyrimidin-2-yl]-propanoic acid

Product 2

HCID 9828589N-[1-(2,3-dichlorobenzyl)pyrrolidin-3-(RS)-ylmethyl]-3-[5-(4-methoxyphenyl)pyrimidin-2-yl]propionamide Hydrochloride SaltYield 69%HCID 9828590N-(1-(2,3-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl)-3-(5-(4-methoxyphenyl)pyrimidin-2-yl)propionamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.29 g, 1.5 mmol, 1.5 equiv.) was added to a suspension of 3-[4-(4-methoxyphenyl)pyrimidin-2-yl]-propanoic acid (0.26 g, 1.0 mmol, 1.0 equiv.), 3-(RS)-aminomethyl-1-(2,3-dichlorobenzyl)-pyrrolidine (0.26 g, 1.0 mmol), 1-hydroxybenzotriazole hydrate (0.20 g, 1.5 mmol, 1.5 equiv.), and diisopropylethylamine (0.44 mL, 2.5 mmol, 2.5 equiv.) in chloroform (2 mL). After stirring overnight at room temperature, the reaction mixture was diluted with ethyl acetate, washed sequentially with 1 M sodium hydroxide, water, 1 M hydrochloric acid, water and brine, then dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (0→10% methanol in methylene chloride). Clean fractions containing the desired product were combined and concentrated, diluted with dioxane and treated with 4 M HCl (0.2 mL) in dioxane. The solution was concentrated under high vacuum to give N-(1-(2,3-dichlorobenzyl)-pyrrolidin-3-(RS)-ylmethyl)-3-(5-(4-methoxyphenyl)pyrimidin-2-yl)propionamide as the HCl salt (185 mg).

Workup

  1. washwashed sequentially with 1 M sodium hydroxide, water, 1 M hydrochloric acid, water and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography (0→10% methanol in methylene chloride)
  5. additionClean fractions containing the desired product
  6. concentrationconcentrated
  7. additiondiluted with dioxane
  8. additiontreated with 4 M HCl (0.2 mL) in dioxane
  9. concentrationThe solution was concentrated under high vacuum

Sources & evidence

ORD record
ord-2cab1368e1bc492188f69efe857f73bb
Source dataset
uspto-grants-2000_12
Patent number
US06166015

Reaction notes

Loading…