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

HRID 1925068Notes

Reaction equation

HRID 1925068 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:8](=[O:18])[NH:9][C:10](=[O:17])[N:11]([CH2:13][CH2:14][CH:15]=O)[CH:12]=2)[S:5][CH:6]=1.C(O)(=O)C.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:30]=[CH:29][C:28]([C@:31]23[CH2:36][C@H:35]2[CH2:34][NH:33][CH2:32]3)=[CH:27][CH:26]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.C(#N)C>[CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:8](=[O:18])[NH:9][C:10](=[O:17])[N:11]([CH2:13][CH2:14][CH2:15][N:33]3[CH2:34][C@H:35]4[C@:31]([C:28]5[CH:27]=[CH:26][C:25]([C:24]([F:23])([F:38])[F:37])=[CH:30][CH:29]=5)([CH2:36]4)[CH2:32]3)[CH:12]=2)[S:5][CH:6]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 594483593-[5-(4-methyl-1,3-thiazol-2-yl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]propanal

Product 1

HCID 252534445-(4-methyl-1,3-thiazol-2-yl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedioneYield 13.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6342AcetonitrileSolvent

Procedure

3-[5-(4-methyl-1,3-thiazol-2-yl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]propanal (Prep.45, 0.109 mmol) was suspended in 1,2-Dichloroethane (DCE) (1 ml) and Acetonitrile (1 ml). Acetic acid (9.36 μl, 0.164 mmol) followed by (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (P4 24.77 mg, 0.109 mmol) were added and the mixture was stirred at rt for 20 minutes. Then the resulting solution was cooled to 0° C. and SODIUM TRIACETOXYBOROHYDRIDE (25.4 mg, 0.120 mmol) was added. The mixture was allowed to reach r.t. under stirring and left at rt overnight. The mixture was treated with NaHCO3 aqueous saturated solution (5 mL) and extracted with EtOAc (3×5 mL). The organic was dried (Na2SO4 and rotary) to afford a yellow solid that was submitted to LC preparative purification. Fractions were collected, dried under vacuum to afford the title compound as a white solid (6.8 mg, 12%).

Workup

  1. additionwere added
  2. temperatureThen the resulting solution was cooled to 0° C.
  3. customto reach r.t.
  4. stirringunder stirring
  5. waitleft at rt overnight
  6. extractionextracted with EtOAc (3×5 mL)
  7. dry with materialThe organic was dried (Na2SO4 and rotary)
  8. customto afford a yellow solid
  9. customthat was submitted to LC preparative purification
  10. customFractions were collected
  11. customdried under vacuum

Sources & evidence

ORD record
ord-af7abc6fbe6a4dc897783fba03ac08e6
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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