Hydrochloric Acid → 5-(6-methyl-2-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 12778Notes

Reaction equation

HRID 12778 reaction equation
[ClH:1].[CH3:2][C:3]1[N:8]=[C:7]([C:9]2[C:10](=[O:16])[NH:11][C:12](=[O:15])[NH:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=1.[Cl:17][CH2:18][CH2:19][CH2:20][N:21]1[CH2:26][C@H:25]2[C@:23]([C:27]3[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=3)([CH2:24]2)[CH2:22]1.CCN(C(C)C)C(C)C.Cl.O1CCOCC1>CS(C)=O.O>[ClH:17].[ClH:1].[CH3:2][C:3]1[N:8]=[C:7]([C:9]2[C:10](=[O:16])[NH:11][C:12](=[O:15])[N:13]([CH2:18][CH2:19][CH2:20][N:21]3[CH2:26][C@H:25]4[C@:23]([C:27]5[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:29][CH:28]=5)([CH2:24]4)[CH2:22]3)[CH:14]=2)[CH:6]=[CH:5][CH:4]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 59337588(1S,5R)-3-(3-chloropropyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 686903115-(6-Methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dione hydrochloride

Product 1

HCID 686879845-(6-methyl-2-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 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A solution of 5-(6-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dione hydrochloride (Prep50, 171 mg, 0.72 mmol), (1S,5R)-3-(3-chloro-propyl)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep13, 240 mg, 0.79 mmol), and DIPEA (278 μl, 2.2 mmol) in DMSO (3 mL) was heated at 125° C. for 3 hours in a microwave oven. Water was added and the product was extracted with ethyl acetate. The crude was purified by preparative LC/MS followed by SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5 The free base obtained was treated with 4N HCl in dioxane (2 eq), to give the title compound as a white powder. (40 mg)

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. customThe crude was purified by preparative LC/MS
  3. washwashing with MeOH
  4. washeluting with MeOH/NH3 95:5 The free base
  5. customobtained

Sources & evidence

ORD record
ord-aaf42f60312a4074a0af91217109f121
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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