Acetic Acid → 2,4-dioxo-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile hydrochloride

HRID 12765노트

반응식

HRID 12765 반응식
[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]1[CH2:11][CH2:12][CH2:13][CH:14]=O.[F:16][C:17]([F:31])([F:30])[C:18]1[CH:23]=[CH:22][C:21]([C@:24]23[CH2:29][C@H:28]2[CH2:27][NH:26][CH2:25]3)=[CH:20][CH:19]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:50]C(Cl)C>O>[ClH:50].[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]1[CH2:11][CH2:12][CH2:13][CH2:14][N:26]1[CH2:27][C@H:28]2[C@:24]([C:21]3[CH:20]=[CH:19][C:18]([C:17]([F:16])([F:31])[F:30])=[CH:23][CH:22]=3)([CH2:29]2)[CH2:25]1

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 589942302,4-Dioxo-1-(4-oxo-butyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrileHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

생성물 1

HCID 686937242,4-dioxo-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile hydrochloride수율 53%

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
0 °C

실험 절차

To a solution of 2,4-dioxo-1-(4-oxo-butyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (Prep55, 70 mg, 0.34 mmol) in dichloroethane (5 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 76 mg, 0.34 mmol) was added. The suspension was cooled at 0° C. and then AcOH (30 mg, 0.68 mmol) and NaBH(AcO)3 (79 mg, 0.38 mmol) were added and the mixture stirred at 0° C. for 4 hours. Water was added and the solvent was evaporated under vacuum, the residue re-dissolved in ethyl acetate and the mixture washed with aqueous saturated NaHCO3 solution. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1) to give the title compound as a white solid (86 mg, 53% yield) as free base

후처리

  1. customthe solvent was evaporated under vacuum
  2. dissolutionthe residue re-dissolved in ethyl acetate
  3. washthe mixture washed with aqueous saturated NaHCO3 solution
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1)

출처 및 근거

ORD 기록
ord-f6673334702b4bd89781c4b98bd8b4ab
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

반응 노트

불러오는 중…