Sodium Methoxide → (R)-N-{4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}quinuclidine-3-amine

HRID 1925214Notes

Reaction equation

HRID 1925214 reaction equation
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([NH:10][C:11]([NH2:13])=[NH:12])[CH2:3]2.C[O-].[Na+].CN(C)[CH:19]=[CH:20][C:21]([C:23]1[N:30]2[C:26]([O:27][CH:28]=[CH:29]2)=[N:25][C:24]=1[C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)=O>C(O)C>[F:37][C:34]1[CH:33]=[CH:32][C:31]([C:24]2[N:25]=[C:26]3[N:30]([C:23]=2[C:21]2[CH:20]=[CH:19][N:13]=[C:11]([NH:10][C@@H:4]4[CH:5]5[CH2:6][CH2:7][N:2]([CH2:9][CH2:8]5)[CH2:3]4)[N:12]=2)[CH:29]=[CH:28][O:27]3)=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 675198943-(Dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-oneHCID 178479392HCID 178479392, compound

Product 1

HCID 16726810(R)-N-{4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}quinuclidine-3-amineYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 5 L 3-neck round bottom flask is charged with the N-1-azabicyclo[2.2.2]oct-3-ylguanidine hydrochloride (261.5 g, 1.277 mol) and absolute ethanol. Sodium methoxide (21% by weight) (405 ml, 1.08 mol) is added dropwise over 15 min. The 3-(dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-one (232.1 g, 0.776 mol) is then added in portions so that no reaction mixture temperature change is observed. The reaction mixture is then refluxed for 5 hours and cooled to room temperature. Solvent is removed in vacuo and the residue partitioned between 1N NaOH and ethyl acetate. The resulting solids are filtered, washed with water, ethyl acetate, and then dried. The solids are then mostly dissolved in hot isopropyl alcohol and filtered through celite while hot. The isopropyl alcohol solution is concentrated to dryness and the solids dried under vacuum to give the desired pyrimidine compound (143.8 g) as a tan solid in 46% yield.

Workup

  1. temperatureThe reaction mixture is then refluxed for 5 hours
  2. customSolvent is removed in vacuo
  3. customthe residue partitioned between 1N NaOH and ethyl acetate
  4. filtrationThe resulting solids are filtered
  5. washwashed with water, ethyl acetate
  6. customdried
  7. dissolutionThe solids are then mostly dissolved in hot isopropyl alcohol
  8. filtrationfiltered through celite while hot
  9. concentrationThe isopropyl alcohol solution is concentrated to dryness
  10. customthe solids dried under vacuum

Sources & evidence

ORD record
ord-480894900f1944e3888a0b59ddb4e7f8
Source dataset
uspto-grants-2012_05
Patent number
US08178672B2

Reaction notes

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