1,4-Dioxane → Hydrochloric Acid

HRID 12773Notes

Reaction equation

HRID 12773 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[C:8](=[O:17])[NH:7][C:6]1=[O:18].[F:19][C:20]([F:34])([F:33])[C:21]1[CH:26]=[CH:25][C:24]([C@:27]23[CH2:32][C@H:31]2[CH2:30][NH:29][CH2:28]3)=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C.O1CCOCC1>CCO>[ClH:1].[ClH:1].[ClH:1].[N:13]1[CH:14]=[CH:15][CH:16]=[C:11]([C:9]2[C:8](=[O:17])[NH:7][C:6](=[O:18])[N:5]([CH2:4][CH2:3][CH2:2][N:29]3[CH2:30][C@H:31]4[C@:27]([C:24]5[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:34])[F:33])=[CH:26][CH:25]=5)([CH2:32]4)[CH2:28]3)[CH:10]=2)[CH:12]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 589941771-(3-Chloro-propyl)-5-pyridin-3-yl-1H-pyrimidine-2,4-dioneHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 2

HCID 313Hydrochloric AcidHCID 686928765-(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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 1-(3-chloro-propyl)-5-pyridin-3-yl-1H-pyrimidine-2,4-dione (Prep43, 92 mg, 0.34 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 68 mg, 0.34 mmol), and DIPEA (134 μl, 1 mmol) in absolute EtOH (3 mL) was placed in a microwave oven and irradiated at 130° C. for 3 hours. The solvent was removed under vacuum and the residue was partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4), filtered and evaporated. The residue was purified by preparative LC-MS. After treatment with 4N HCl in dioxane (2 eq), the title compound was obtained (5 mg, 4% yield)

Workup

  1. customirradiated at 130° C. for 3 hours
  2. customThe solvent was removed under vacuum
  3. customthe residue was partitioned between water and ethyl acetate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by preparative LC-MS

Sources & evidence

ORD record
ord-64e8b09e11914286a0a842196707cf5b
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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