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

HRID 12764노트

반응식

HRID 12764 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][CH:13]=O.[F:15][C:16]([F:30])([F:29])[C:17]1[CH:22]=[CH:21][C:20]([C@:23]23[CH2:28][C@H:27]2[CH2:26][NH:25][CH2:24]3)=[CH:19][CH:18]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:49]C(Cl)C>>[ClH:49].[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][N:25]1[CH2:26][C@H:27]2[C@:23]([C:20]3[CH:19]=[CH:18][C:17]([C:16]([F:15])([F:30])[F:29])=[CH:22][CH:21]=3)([CH2:28]2)[CH2:24]1

참가 물질

6

반응물 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 589942042,4-Dioxo-1-(3-oxo-propyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrileHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

생성물 1

HCID 686933782,4-dioxo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile hydrochloride수율 38%

실험 절차

To a solution of 2,4-dioxo-1-(3-oxo-propyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (Prep35, 90 mg, 0.47 mmol) in dichloroethane (8 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 106 mg, 0.47 mmol), AcOH (42 mg, 0.7 mmol) and NaBH(AcO)3 (198 mg, 0.94 mmol) were added and the mixture was stirred at room temperature overnight. The solvent was evaporated under vacuum, the residue redissolved in ethyl acetate and the obtained 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 free base of the title compound as a white solid (70 mg, 38% yield).

후처리

  1. customThe solvent was evaporated under vacuum
  2. dissolutionthe residue redissolved in ethyl acetate
  3. washthe obtained 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-a14a8617c08141e78bf3ffd25e5ba2bd
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

반응 노트

불러오는 중…