Diisopropylethylamine → 6-Fluoro-3-[((2S)-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]pyrazolo[1,5-a]pyrimidine

HRID 418303Notes

Reaction equation

HRID 418303 reaction equation
[Li].[F:2][C:3]1[CH:4]=[N:5][C:6]2[N:7]([N:9]=[CH:10][C:11]=2[C:12]([O-:14])=O)[CH:8]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:48][C@@H:49]1[NH:54][CH2:53][CH2:52][N:51]([S:55]([C:58]2[CH:63]=[CH:62][C:61]([C:64]([F:67])([F:66])[F:65])=[CH:60][CH:59]=2)(=[O:57])=[O:56])[CH2:50]1>CN(C=O)C>[F:2][C:3]1[CH:4]=[N:5][C:6]2[N:7]([N:9]=[CH:10][C:11]=2[C:12]([N:54]2[CH2:53][CH2:52][N:51]([S:55]([C:58]3[CH:59]=[CH:60][C:61]([C:64]([F:67])([F:65])[F:66])=[CH:62][CH:63]=3)(=[O:56])=[O:57])[CH2:50][C@@H:49]2[CH3:48])=[O:14])[CH:8]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 3028194LithiumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 591520706-Fluoropyrazolo[1,5-a]pyrimidine-3-carboxylateHCID 59152086(S)-3-Methyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)piperazine

Product 1

HCID 666495276-Fluoro-3-[((2S)-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]pyrazolo[1,5-a]pyrimidineYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The lithium salt of 6-fluoropyrazolo[1,5-a]pyrimidine-3-carboxylate (117 mg, 0.63 mmol) (may be prepared as described in Description 16) was weighed into a vial with HATU (247 mg, 0.65 mmol), suspended in DMF (2 ml) and treated with DIPEA (0.170 ml, 0.97 mmol). This mixture was stirred about 15 min at ambient temperature. (3S)-3-Methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (may be prepared as described in Description 2) (100 mg, 0.32 mmol) was added and stirring was continued for 3 h at ambient temperature. The reaction mixture was partitioned between DCM and sat. aq. NaHCO3 solution (10 ml each). The layers were separated (hydrophobic frit) and the aqueous layer was washed with further DCM (2×5 ml). The combined organic layers were concentrated to leave an orange gum. Purification by MDAP gave the title compound (112 mg, 0.24 mmol, 73% yield) as an orange solid.

Workup

  1. stirringstirring
  2. waitwas continued for 3 h at ambient temperature
  3. customThe reaction mixture was partitioned between DCM and sat. aq. NaHCO3 solution (10 ml each)
  4. customThe layers were separated (hydrophobic frit)
  5. washthe aqueous layer was washed with further DCM (2×5 ml)
  6. concentrationThe combined organic layers were concentrated
  7. customto leave an orange gum
  8. customPurification by MDAP

Sources & evidence

ORD record
ord-1efe19f27bfc4c12926717863e50e24d
Source dataset
uspto-grants-2012_01
Patent number
US08093249B2

Reaction notes

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