Trifluoroacetic acid → [8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(1-piperidin-4-yl-1H-pyrazol-4-yl)-amine

HRID 1889990Notes

Reaction equation

HRID 1889990 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([NH:19][C:20]3[N:38]=[C:23]4[C:24]([C:28]5[CH:33]=[CH:32][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:30][CH:29]=5)=[CH:25][CH:26]=[CH:27][N:22]4[N:21]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:37][S:34]([C:31]1[CH:30]=[CH:29][C:28]([C:24]2[C:23]3[N:22]([N:21]=[C:20]([NH:19][C:17]4[CH:16]=[N:15][N:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)[CH:18]=4)[N:38]=3)[CH:27]=[CH:26][CH:25]=2)=[CH:33][CH:32]=1)(=[O:36])=[O:35]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 674813844-{4-[8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine-2-ylamino]-pyrazol-1-yl}-piperidin-1-carboxylic acid tert-butyl ester

Product 1

HCID 67481518[8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(1-piperidin-4-yl-1H-pyrazol-4-yl)-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a well stirred solution of 4-{4-[8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-pyrazol-1-yl}-piperidin-1-carboxylic acid tert-butyl ester (100 mg, 0.186 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (0.65 mL, 8.77 mmol) dropwise at room temperature. After 1 h, the reaction mixture was evaporated in vacuo and partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic layer was separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and evaporated. The crude product was crystallized from a mixture of dichloromethane, methanol, ether and hexane. [8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(1-piperidin-4-yl-1H-pyrazol-4-yl)-amine was isolated as a greenish-yellow solid (58 mg, 71%). MP=Softened at 154-159° C. then melted at 211-213° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.37 (s, 1H), 8.79 (d, J=6.48 Hz, 1H), 8.42 (d, J=7.96 Hz, 2H), 8.06 (d, J=7.97 Hz, 2H), 7.94 (d, J=7.45 Hz, 1H), 7.83 (s, 1H), 7.49 (s, 1H), 7.12 (t, J=7.04 Hz, 1H), 4.14 (t, J=11.29 Hz, 1H), 3.29 (s, 3H), 3.035 (d, J=12.28 Hz, 2H), 2.58 (t, J=12.16 Hz, 2H), 1.935 (d, J=11.41 Hz), 1.68-182 (m, 2H). MS=438 (MH)+.

Workup

  1. customthe reaction mixture was evaporated in vacuo
  2. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate solution
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted twice with dichloromethane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was crystallized from a mixture of dichloromethane, methanol, ether and hexane

Sources & evidence

ORD record
ord-0ca2e0ddb54f4b0f8a94f9c1f0b545e0
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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