Ethanol → HCID 53354117, compound

HRID 451464Notes

Reaction equation

HRID 451464 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH:13]([F:15])[CH2:12][N:11]3[N:16]=[C:17]([NH2:19])[N:18]=[C:10]23)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:20][C:21]1[N:25]=[C:24]([N:26]2[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]2)[S:23][N:22]=1.[BH4-].[Na+].C(O)C>ClC(Cl)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH:13]([F:15])[CH2:12][N:11]3[N:16]=[C:17]([NH:19][CH:29]4[CH2:28][CH2:27][N:26]([C:24]5[S:23][N:22]=[C:21]([CH3:20])[N:25]=5)[CH2:31][CH2:30]4)[N:18]=[C:10]23)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 592585101-(3-Methyl-1,2,4-thiadiazol-5-yl)piperidin-4-one2×HCID 67342019[1,2,4]Triazolo[1,5-a]pyridin-2-amine, 8-(3,4-difluorophenyl)-6-fluoro-5,6,7,8-tetrahydro-

Product 1

HCID 53354117HCID 53354117, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 8-(3,4-difluorophenyl)-6-fluoro-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (74 mg, 276 μmol), 1-(3-methyl-1,2,4-thiadiazol-5-yl)piperidin-4-one (82 mg, 414 μmol) and titanium(IV) isopropoxide (240 mg, 253 μL, 828 μmol) dissolved in dichloroethane (6 mL) was heated to 85° C. for 12 hours. Further 1-(3-methyl-1,2,4-thiadiazol-5-yl)piperidin-4-one (54 mg, 276 μmol) was added and stirred at 85° C. for another two hours. The reaction mixture was cooled to 50° C., sodium borohydride (41.7 mg, 1.1 mmol) and ethanol (3 mL) were added and stirred at 50° C. for one hour. The solvent was evaporated, the residue extracted with 2 N Na2CO3 solution and ethyl acetate. The organic layers were combined, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane) and then by preparative HPLC. The title compound was obtained as light green foam (37.1 mg, 30%).

Workup

  1. temperatureThe reaction mixture was cooled to 50° C.
  2. stirringstirred at 50° C. for one hour
  3. customThe solvent was evaporated
  4. extractionthe residue extracted with 2 N Na2CO3 solution and ethyl acetate
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane)

Sources & evidence

ORD record
ord-dd568c35d06346719956b28b21793a39
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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