HCID 59234644, compound → HCID 66915773, compound

HRID 1697859Notes

Reaction equation

HRID 1697859 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:13]=[N:14][C:15]([CH3:18])=[CH:16][CH:17]=2)[C:7]1=[O:19].[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>CN(C=O)C>[ClH:1].[ClH:1].[CH3:18][C:15]1[N:14]=[CH:13][C:12]([C:8]2[C:7](=[O:19])[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:30]3[CH2:31][C@H:32]4[C@:28]([C:25]5[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=5)([CH2:33]4)[CH2:29]3)[CH:11]=[CH:10][CH:9]=2)=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 59234644HCID 59234644, compoundHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 66915773HCID 66915773, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

TEA (0.056 ml, 0.4 mmol) was added to a solution of 1-(4-chlorobutyl)-6′-methyl-3,3′-bipyridin-2(1H)-one (55 mg, 0.2 mmol, Prep8) and (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Prep4, 70 mg, 0.31 mmol, reference procedure for preparation also reported in WO 2005080382) in anhydrous DMF (2 ml). The reaction mixture was heated at 90° C. for 1 hour and then at 100° C. for 24 hours, quenched with water and extracted with ethyl acetate. The combined organics layers were dried (Na2SO4) and concentrated in vacuo. The crude product was purified by SCX cartridge (eluting with methanol followed by 2N ammonia solution in methanol) and then by SPE cartridge eluting with a gradient of methanol in DCM (from 0 to 5%) to afford the free base of the title compound (19 mg, 20%).

Workup

  1. customquenched with water
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organics layers were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by SCX cartridge (eluting with methanol followed by 2N ammonia solution in methanol)
  6. washby SPE cartridge eluting with a gradient of methanol in DCM (from 0 to 5%)

Sources & evidence

ORD record
ord-73b10d99dde242efbe14b87c28d8f1af
Source dataset
uspto-grants-2012_04
Patent number
US08163927B2

Reaction notes

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