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

HRID 1925214노트

반응식

HRID 1925214 반응식
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

참가 물질

5

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-480894900f1944e3888a0b59ddb4e7f8
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178672B2

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