Triphenylphosphine → HCID 66788141, compound

HRID 2381124Notes

Reaction equation

HRID 2381124 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH3:15][N:16]1[C:20]([CH2:21][CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][N:33]([C:36]4[CH2:37][CH2:38][C:39]5[N:40]([C:42]([C:45]([F:48])([F:47])[F:46])=[N:43][N:44]=5)[N:41]=4)[CH2:32][CH2:31]3)=[CH:26][CH:25]=2)=CC=N1.OCCCN1C[CH2:57][N:56]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:55][CH2:54]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[F:48][C:45]([F:47])([F:46])[C:42]1[N:40]2[N:41]=[C:36]([N:33]3[CH2:34][CH2:35][N:30]([C:27]4[CH:26]=[CH:25][C:24]([O:23][CH2:22][CH2:21][CH2:20][N:16]5[CH2:15][CH2:57][N:56]([C:59]([O:61][C:62]([CH3:63])([CH3:65])[CH3:64])=[O:60])[CH2:55][CH2:54]5)=[CH:29][CH:28]=4)[CH2:31][CH2:32]3)[CH:37]=[CH:38][C:39]2=[N:44][N:43]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 162178001-Boc-4-(3-hydroxypropyl)piperazineHCID 46893851HCID 46893851, compound

Product 1

HCID 66788141HCID 66788141, compoundYield 45.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIAD (3.24 mL, 16.47 mmol) was added dropwise to 4-{4-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl}phenol (obtained as described in Example 16, preparation of starting materials) (5 g, 13.72 mmol), tert-butyl 4-(3-hydroxypropyl)piperazine-1-carboxylate (CAS 132710-90-8, 5.03 g, 20.59 mmol) and triphenylphosphine (5.40 g, 20.59 mmol) in THF (50 mL) at 0° C. under nitrogen. The resulting solution was stirred at ambient temperature for 16 hours. The reaction mixture was evaporated to dryness and redissolved in DCM (100 mL), and washed sequentially with 2M NaOH (100 mL) and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, eluting with EtOAc. Pure fractions were evaporated to dryness to give tert-butyl 4-[3-(4-{4-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl}phenoxy)propyl]piperazine-1-carboxylate (3.66 g, 45%).

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionredissolved in DCM (100 mL)
  3. washwashed sequentially with 2M NaOH (100 mL) and saturated brine (100 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography
  9. washeluting with EtOAc
  10. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-a650c6b4f1f248f3b5cd56c0eeb0538e
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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