Acetic Acid → HCID 25252823, compound

HRID 1925046Notes

Reaction equation

HRID 1925046 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:8]2[C:9](=O)[N:10]([C:19]([C:21]3[CH:26]=CC=CC=3)=O)[C:11](=[O:18])[N:12](C(C)C=O)[CH:13]=2)[S:5][C:6]=1[CH3:7].[F:28][C:29]([F:43])([F:42])[C:30]1[CH:35]=[CH:34][C:33]([C@:36]23[CH2:41][C@H:40]2[CH2:39][NH:38][CH2:37]3)=[CH:32][CH:31]=1.C(O)(=[O:46])C.[Na]>C(#N)C.CCOC(C)=O.ClCCCl>[CH3:1][C:2]1[N:3]=[C:4]([C:8]2[C:13](=[O:46])[NH:12][C:11](=[O:18])[N:10]([CH2:19][CH2:21][CH2:26][N:38]3[CH2:39][C@H:40]4[C@:36]([C:33]5[CH:32]=[CH:31][C:30]([C:29]([F:28])([F:42])[F:43])=[CH:35][CH:34]=5)([CH2:41]4)[CH2:37]3)[CH:9]=2)[S:5][C:6]=1[CH3:7]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5360545SodiumHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 86644393HCID 86644393, compound

Product 1

HCID 25252823HCID 25252823, compoundYield 74.9%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

[5-(4,5-dimethyl-1,3-thiazol-2-yl)-2,4-dioxo-3-(phenylcarbonyl)-3,4-dihydro-1(2H)-pyrimidinyl]propanal (Prep18, 0.098 mmol from previous reaction considered quantitative) was dissolved in Acetonitrile (1.500 ml). (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Prep4, 0.022 g, 0.098 mmol) was added and to the resulting slurry 1,2-Dichloroethane (DCE) (1.5 ml) and Acetic acid (0.011 ml, 0.196 mmol) were added. The resulting clear and dark yellow solution was stirred at rt for 10 minutes then it was cooled to 0° C. and sodium triacetoxyborohydryde (0.023 g, 0.108 mmol) was added in one portion. The mixture was stirred while the temperature slowly rose to rt (ca 5 hrs). The mixture was diluted with EtOAc (20 mL) washed with aqueous saturated NaHCO3 and extracted with EtOAc (2×5 mL). The organics were combined and dried (Na2O4, rotary evaporator) to afford a crude that was purified by silica chromatography, eluting with DCM:MeOH 100:0 to 9:1 to afford a yellow foam that was purified by SCX (5 g) eluting with DCM, MeOH, Ammonia 1M in MeOH (10 mL each) to afford 36 mg of compound that was further purified by Fraction Lynx. Product fraction was dried to afford 5 mg of impure title compound that was filtered through an SCX cartridge (500 mg) eluting with DCM, MeOH, Ammonia 2M in MeOH. Fraction from ammonia was dried to afford the title compound as a white solid (3 mg)

Workup

  1. additionwere added
  2. temperatureit was cooled to 0° C.
  3. stirringThe mixture was stirred while the temperature
  4. customslowly rose to rt
  5. custom(ca 5 hrs)
  6. washwashed with aqueous saturated NaHCO3
  7. extractionextracted with EtOAc (2×5 mL)
  8. customdried
  9. custom(Na2O4, rotary evaporator)
  10. customto afford a crude that
  11. customwas purified by silica chromatography
  12. washeluting with DCM:MeOH 100:0 to 9:1
  13. customto afford a yellow foam that
  14. customwas purified by SCX (5 g)
  15. washeluting with DCM, MeOH, Ammonia 1M in MeOH (10 mL each)

Sources & evidence

ORD record
ord-be3e741cf2f8452fa1ae25e8d1162091
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

Loading…