1,1-Dichloroethane → 5-(4-methyl-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

HRID 12808노트

반응식

HRID 12808 반응식
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH:16]=O)[CH:13]=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+].[Cl:52]C(Cl)C>CC(O)=O>[ClH:52].[ClH:52].[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH2:16][N:30]2[CH2:31][C@H:32]3[C@:28]([C:25]4[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=4)([CH2:33]3)[CH2:29]2)[CH:13]=1

참가 물질

7

반응물 5

HCID 63651,1-DichloroethaneHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 58994157HCID 58994157, 화합물HCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

생성물 1

HCID 686919985-(4-methyl-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride수율 27%

시약·촉매·용매 1

HCID 176Acetic Acid용매

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온도
0 °C

실험 절차

A solution of 3-[5-(4-Methyl-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep113, 84 mg, 0.32 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 74 mg, 0.32 mmol), and AcOH (23 μl) in dichloroethane (4 ml) was cooled to 0° C. NaBH(AcO)3 (72 mg, 0.34 mmol) was added portionwise. The mixture was stirred at 0° C. for 2 hours and at room temperature for 30 minutes and then basified with 1N NaOH. The product was extracted with DCM, the organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred for 5 hours in presence of PS-isocyanate. The mixture was filtered and the solvent was evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98:2:0.2) to give 41 mg of the free base of title compound (27% yield).

후처리

  1. extractionThe product was extracted with DCM
  2. dry with materialthe organic phase was dried (Na2SO4)
  3. customevaporated
  4. dissolutionThe residue was redissolved in DCM
  5. stirringstirred for 5 hours in presence of PS-isocyanate
  6. filtrationThe mixture was filtered
  7. customthe solvent was 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-2e06fa0ac03542c299b6b396a177ad76
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

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