Nicotinic Acid → (6-Hydroxy-pyridin-3-yl)-(S)(+)-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone

HRID 552584

Reaction equation

HRID 552584 reaction equation
N=C=N.[C:4]([OH:12])(=O)[C:5]1[CH:10]=[CH:9][CH:8]=[N:7][CH:6]=1.[NH:13]1[CH2:17][CH2:16][CH2:15][C@H:14]1[CH2:18][N:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1.C1C=CC2N([OH:33])N=NC=2C=1.C(N(CC)CC)C>C(Cl)(Cl)Cl.C(O)CCC.CC#N>[OH:33][C:8]1[N:7]=[CH:6][C:5]([C:4]([N:13]2[CH2:17][CH2:16][CH2:15][C@H:14]2[CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:12])=[CH:10][CH:9]=1

Participants

7

Reactant 5

HCID 938Nicotinic AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 853152(S)-(+)-1-(2-Pyrrolidinylmethyl)pyrrolidine

Product 1

HCID 178519724(6-Hydroxy-pyridin-3-yl)-(S)(+)-(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanoneYield 73%

Reagents, catalysts & solvents 1

HCID 131728932CHCl3 BuOH MeCNSolvent

Procedure

PS-carbodiimide (1.39 mmol/g) resin beads (2.1 g, 3 mmol) are added to a 10 mL CHCl3/BuOH/MeCN (5:1:1) mixture of nicotinic acid (278 mg, 2 mmol), (S)(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (231 mg, 1.5 mmol), HOBt (300 mg, 2.2 mmol), and triethylamine (0.30 mL, 2.2 mmol). The mixture is shaken at room temperature for 3 days. The reaction mixture is filtered and the beads are washed alternately with MeOH, then CH2Cl2, and the filtrate is concentrated in vacuo. The crude material product is partially purified by a SCX column (MeOH wash, elution with 2M NH3 in MeOH. Further purification is accomplished using silica-gel column chromatography (gradient: 100% CH2Cl2 to 10% 2M NH3 in MeOH/CH2Cl2) to give the title compound (200 mg, 73%). MS (ES+) 276.1 (M+H)+.

Workup

  1. filtrationThe reaction mixture is filtered
  2. washthe beads are washed alternately with MeOH
  3. concentrationCH2Cl2, and the filtrate is concentrated in vacuo
  4. customThe crude material product is partially purified by a SCX column (MeOH
  5. washwash
  6. washelution with 2M NH3 in MeOH
  7. customFurther purification

Sources & evidence

ORD record
ord-31969ee1edb848ccac5c2bc1371d3bec
Source dataset
uspto-grants-2011_05
Patent number
US07951826B2

Linked notes

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