Sodium Hydroxide → 5-(6-chloro-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

HRID 12801노트

반응식

HRID 12801 반응식
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH:16]=O)[CH:13]=2)=[CH:4][CH:3]=1.[F:20][C:21]([F:35])([F:34])[C:22]1[CH:27]=[CH:26][C:25]([C@:28]23[CH2:33][C@H:32]2[CH2:31][NH:30][CH2:29]3)=[CH:24][CH:23]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClC(Cl)C.CO.[Cl-].[Na+].O.CC(O)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH2:16][N:30]3[CH2:31][C@H:32]4[C@:28]([C:25]5[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=5)([CH2:33]4)[CH2:29]3)[CH:13]=2)=[CH:4][CH:3]=1

참가 물질

8

반응물 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 589942093-[5-(6-Chloro-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

생성물 1

HCID 247582225-(6-chloro-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione수율 34.8%

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 22036585Dichloroethane methanol용매HCID 57417360Sodium chloride; water용매

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온도
0 °C

실험 절차

A solution of 3-[5-(6-Chloro-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep93, 0.82 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 186 mg, 0.82 mmol), and AcOH (58 μl) in dichloroethane-MeOH (10-0.1, 8 ml) was cooled to 0° C. NaBH(AcO)3 (182 mg, 0.86 mmol) was added portionwise. The mixture was stirred at 0° C. for further one hour and then basified with 1N NaOH. Brine was added and the product extracted with DCM. The organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred overnight in the presence of PS-isocyanate. The mixture was filtered and the solvent evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98:2:0.2) to give 140 mg of the title compound (34% yield).

후처리

  1. extractionthe product extracted with DCM
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. dissolutionThe residue was redissolved in DCM
  5. stirringstirred overnight in the presence of PS-isocyanate
  6. filtrationThe mixture was filtered
  7. customthe solvent evaporated
  8. customThe crude was purified by flash chromatography
  9. washeluting with DCM-MeOH—NH4OH (98:2:0.2)

출처 및 근거

ORD 기록
ord-155b10483edf4f4aba22277effd8460e
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

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