Sodium Hydroxide → HCID 86615961, compound

HRID 12795Notes

Reaction equation

HRID 12795 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH:16]=O)[CH:13]=1.[F:20][C:21]([F:35])([F:34])[C:22]1[CH:27]=[CH:26][C:25]([C@:28]23[CH2:33][C@H:32]2[CH2:31][NH:30][CH2:29]3)=[CH:24][CH:23]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+].C(Cl)[Cl:53].CO>CC(O)=O>[ClH:53].[ClH:53].[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH2:16][N:30]2[CH2:31][C@H:32]3[C@:28]([C:25]4[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=4)([CH2:33]3)[CH2:29]2)[CH:13]=1

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 21226129Dichloromethane methanolHCID 58994175HCID 58994175, compoundHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 86615961HCID 86615961, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

3-[5-(3-Fluoro-pyridin-4-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep69, 63 mg, 0.24 mmol) was dissolved in DCM-MeOH 1-1 (2 ml). The resulting solution was cooled at 0° C. and then (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (54 mg, 0.24 mmol), AcOH (17 μl) and NaBH(AcO)3 (55 mg, 0.26 mmol) were added. The mixture was left to reach room temperature and the stirring was prolonged for further 18 hours. 1N NaOH was added and the product was extracted with DCM. The organic phase was dried (Na2SO4) and evaporated. The crude was redissolved in DCM and treated with PS-isocyanate (300 mg) overnight. The residue was finally purified with SCX cartridge, washing with MeOH and then collecting the product with MeOH—NH4OH (95-5) to give 17 mg of the title compound (16% yield).

Workup

  1. waitThe mixture was left
  2. customto reach room temperature
  3. extractionthe product was extracted with DCM
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. dissolutionThe crude was redissolved in DCM
  7. additiontreated with PS-isocyanate (300 mg) overnight
  8. customThe residue was finally purified with SCX cartridge
  9. washwashing with MeOH
  10. customcollecting the product with MeOH—NH4OH (95-5)

Sources & evidence

ORD record
ord-a63941edc6754ed2b147e6f104c0245a
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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