1-(5-Trifluoromethyl-pyridin-2-yl)-piperazine → (3R)-1-Isopropyl-3-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)piperazine

HRID 549925Notes

Reaction equation

HRID 549925 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[N:7][CH:8]=1.C(OC([N:24]1[CH2:29][CH2:28][N:27]([CH:30]([CH3:32])[CH3:31])[CH2:26][C@@H:25]1[C:33](O)=[O:34])=O)(C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C1COCC1.C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH:30]([N:27]1[CH2:28][CH2:29][NH:24][C@@H:25]([C:33]([N:12]2[CH2:11][CH2:10][N:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][N:7]=3)[CH2:14][CH2:13]2)=[O:34])[CH2:26]1)([CH3:32])[CH3:31]

Participants

6

Reactant 3

HCID 6676181-(5-Trifluoromethyl-pyridin-2-yl)-piperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51440433(2R)-1-(tert-butoxycarbonyl)-4-isopropylpiperazine-2-carboxylic acid

Product 1

HCID 24877110(3R)-1-Isopropyl-3-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)piperazineYield 35.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

1-[5-(Trifluoromethyl)pyridin-2-yl]piperazine (170 mg) and (2R)-1-(tert-butoxycarbonyl)-4-isopropylpiperazine-2-carboxylic acid (200 mg) were dissolved in dry THF (10 ml) followed by addition of N′N-di-isopropylethylamine (0.15 ml) and O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-TetramethylUronium Hexafluorophosphate (307 mg) and the reaction was stirred for 4 hours. The solvent was evaporated under reduced pressure, redissolved in DCM (50 ml) and washed with saturated aqueous NaHCO3 (20 ml). The organic layer was separated on a phase separation cartridge and evaporated. Purification by chromatography (3-10% MeOH:DCM) afforded the crude product (231 mg) as a foam which was then dissolved in TFA/DCM (1:1, 10 ml) and stirred for 30 minutes. The solvents were removed under reduced pressure, the residue taken up in 1M aqueous NaOH (30 ml) and extracted with DCM (2×30 ml). The organic layer was separated on a phase separation cartridge and evaporated. Purification by chromatography (5-25% MeOH:DCM) afforded the title compound (100 mg) as a white foam.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionredissolved in DCM (50 ml)
  3. washwashed with saturated aqueous NaHCO3 (20 ml)
  4. customThe organic layer was separated on a phase separation cartridge
  5. customevaporated
  6. customPurification by chromatography (3-10% MeOH:DCM)
  7. customafforded the crude product (231 mg) as a foam which
  8. stirringstirred for 30 minutes
  9. customThe solvents were removed under reduced pressure
  10. extractionextracted with DCM (2×30 ml)
  11. customThe organic layer was separated on a phase separation cartridge
  12. customevaporated
  13. customPurification by chromatography (5-25% MeOH:DCM)

Sources & evidence

ORD record
ord-beb3de98534544f8983579689a5b7eac
Source dataset
uspto-grants-2011_05
Patent number
US07943768B2

Reaction notes

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