Sodium Hydroxide → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]pyrrolo[1,2-c]pyrimidine-3-carboxamide Hydrochloride

HRID 25156

Reaction equation

HRID 25156 reaction equation
Cl.[CH:2]1[N:7]2[CH:8]=[CH:9][CH:10]=[C:6]2[CH:5]=[C:4]([C:11]([OH:13])=O)[N:3]=1.C1(P([Cl:28])(C2C=CC=CC=2)=O)C=CC=CC=1.Cl.Cl.[NH2:31][C@@H:32]1[CH:37]2[CH2:38][CH2:39][N:34]([CH2:35][CH2:36]2)[CH2:33]1.[OH-].[Na+]>C1COCC1>[ClH:28].[N:34]12[CH2:39][CH2:38][CH:37]([CH2:36][CH2:35]1)[C@@H:32]([NH:31][C:11]([C:4]1[N:3]=[CH:2][N:7]3[CH:8]=[CH:9][CH:10]=[C:6]3[CH:5]=1)=[O:13])[CH2:33]2

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 73910Diphenylphosphinic chlorideHCID 12494972(R)-(+)-3-Aminoquinuclidine DihydrochlorideHCID 69607058Pyrrolo[1,2-c]pyrimidine-3-carboxylic acid hydrochloride

Product 1

HCID 69773092N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]pyrrolo[1,2-c]pyrimidine-3-carboxamide HydrochlorideYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Pyrrolo[1,2-c]pyrimidine-3-carboxylic acid hydrochloride (0.33 g, 1.66 mmol) and TEA (2.0 mL, 14.35 mmol) are dissolved in 15 mL THF. Diphenylphosphinic chloride (0.47 g, 1.99 mmol) is added dropwise. After 1 h, (R)-(+)-3-aminoquinuclidine dihydrochloride is added and the reaction is allowed to stir at RT. After 1 day, 1N NaOH is added and the mixture is extracted with CHCl3. The combined organic layers are dried (MgSO4), filtered and concentrated. The residue is purified by chromatography (Biotage 40S, 90:9:1 CHCl3/MeOH/NH4OH) to afford 0.45 g (100%) of product. The hydrochloride salt is prepared and recrystallized from CH3CN/Et2O.

Workup

  1. waitAfter 1 day
  2. extractionthe mixture is extracted with CHCl3
  3. dry with materialThe combined organic layers are dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by chromatography (Biotage 40S, 90:9:1 CHCl3/MeOH/NH4OH)

Sources & evidence

ORD record
ord-4bcf1dbee79d43acbf8b6721c5e60614
Source dataset
uspto-grants-2005_02
Patent number
US06858613B2

Linked notes

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