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

HRID 12770
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HRID 12770 반응식
I[C:2]1[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][C@H:15]3[C@:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)([CH2:14]3)[CH2:12]2)[CH:7]=1.[N:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>COCCOC.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:29]1[CH:34]=[CH:33][C:32]([C:2]2[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]3[CH2:16][C@H:15]4[C@:13]([C:17]5[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=5)([CH2:14]4)[CH2:12]3)[CH:7]=2)=[CH:31][CH:30]=1
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참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 2734379(Pyridin-4-yl)boronic acidHCID 675197195-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

생성물 1

HCID 247593375-(4-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione
수율 32%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 8857Ethyl Acetate용매HCID 18180031Water 1,2-dimethoxyethane용매

실험 절차

5-Iodo-1-{3-[(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hex-3-yl]-propyl}-1H-pyrimidine-2,4-dione (Prep40, 46 mg, 0.09 mmol) was dissolved in degassed DME-water solution (5-1, 1 mL). Pyridine 4-boronic acid (22 mg, 0.18 mmol), Na2CO3 (20 mg, 0.18 mmol), 2-(dicyclohexylphosphino)biphenyl (7 mg, 0.02 mmol) and Pd(PPh3)4 (20 mg, 0.02 mmol) were added and the mixture was placed in a microwave oven and heated at 150° for 20 minutes. The mixture was diluted with ethyl acetate, and washed with water. The organic phase was dried (Na2SO4) and evaporated; the crude was dissolved in MeOH and loaded on SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5. The residue was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1) to give the title compound (13 mg, 32% yield) as free base.

후처리

  1. customthe mixture was placed in a microwave oven
  2. temperatureheated at 150° for 20 minutes
  3. washwashed with water
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. dissolutionthe crude was dissolved in MeOH
  7. washwashing with MeOH
  8. washeluting with MeOH/NH3 95:5
  9. customThe residue was purified by flash chromatography with DCM-MeOH—NH4OH (99-1-0.1)

출처 및 근거

ORD 기록
ord-d56abf5c040d410d8e4d1de612a724b3
출처 데이터셋
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07727988B2

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