Water → 6-Methyl-3-[(4-{[4-(trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]pyrazolo[1,5-a]pyrimidine

HRID 418300Notes

Reaction equation

HRID 418300 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C1C=CC2N(O)N=NC=2C=1.O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:55][C:56]1[CH:57]=[N:58][C:59]2[N:60]([N:62]=[CH:63][C:64]=2[C:65](O)=[O:66])[CH:61]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[CH3:55][C:56]1[CH:57]=[N:58][C:59]2[N:60]([N:62]=[CH:63][C:64]=2[C:65]([N:15]2[CH2:16][CH2:17][N:12]([S:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:18])[F:19])=[CH:8][CH:7]=3)(=[O:10])=[O:11])[CH2:13][CH2:14]2)=[O:66])[CH:61]=1

Participants

9

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 25545781-[4-(Trifluoromethyl)benzenesulfonyl]piperazineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 64854106-Methylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 591520736-Methyl-3-[(4-{[4-(trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]pyrazolo[1,5-a]pyrimidineYield 51.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (may be prepared as described in Description 1) (100 mg, 0.340 mmol) in DMF (5 ml) was added HOBT.H2O (52.0 mg, 0.340 mmol), HBTU (129 mg, 0.340 mmol), 6-methylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid (60.2 mg, 0.340 mmol) and DIPEA (0.178 ml, 1.019 mmol), in a 2.0-5.0 ml microwave vial. The reaction mixture was stirred for 3 hours at rt. The reaction mixture was transferred to a 100 ml round bottom flask and was reduced to dryness in vacuo. The residue was dissolved in DCM (50 ml) and was transferred to a separating funnel then washed with saturated aq. NaHCO3 solution (5 ml), twice. The organic layer was collected and dried with dried magnesium sulfate. The solid was removed by filtration and the filtrate collected in a 250 ml round bottom flask and reduced to dryness in vacuo. The residue was then dissolved in 1.8 ml (1:1) MeCN/DMSO and purified by MDAP in 2 batches. The fractions containing desired product were combined in a 250 ml round bottom flask and reduced in vacuo to yield the title compound (79 mg).

Workup

  1. customThe reaction mixture was transferred to a 100 ml round bottom flask
  2. customwas transferred to a separating funnel
  3. washthen washed with saturated aq. NaHCO3 solution (5 ml)
  4. customThe organic layer was collected
  5. dry with materialdried with dried magnesium sulfate
  6. customThe solid was removed by filtration
  7. customthe filtrate collected in a 250 ml round bottom flask
  8. dissolutionThe residue was then dissolved in 1.8 ml (1:1) MeCN/DMSO
  9. custompurified by MDAP in 2 batches
  10. additionThe fractions containing desired product
  11. customwere combined in a 250 ml round bottom flask

Sources & evidence

ORD record
ord-51e7c6978d314db28bf2501b89deb2db
Source dataset
uspto-grants-2012_01
Patent number
US08093249B2

Reaction notes

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