Trifluoroacetic acid → 3-(1,3-Benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine

HRID 908385Notes

Reaction equation

HRID 908385 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9]([CH3:26])=[N:10][N:11]([CH:13]3[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]3)[CH:12]=2)=[CH:4][C:3]=1[C:27]1[O:28][C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[N:31]=1.C(O)(C(F)(F)F)=O>ClCCl.C(#N)C>[O:28]1[C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[N:31]=[C:27]1[C:3]1[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([C:8]2[C:9]([CH3:26])=[N:10][N:11]([CH:13]3[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]3)[CH:12]=2)[CH:4]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57687030Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-methyl-pyrazol-1-yl]piperidine-1-carboxylate

Product 1

HCID 425993613-(1,3-Benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amineYield 73.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-methyl-pyrazol-1-yl]piperidine-1-carboxylate (500 mg) in dichloromethane (3 ml) was added TFA (1 ml). The solution was stirred at 25° C. for 2 hours. The mixture was evaporated to dryness, then the residue was diluted in dichloromethane and ammonia in methanol 7N was added. After removal of solvents, the crude product was purified by flash chromatography on silica gel eluting with 10% methanol in dichloromethane followed by 10 to 25% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford a solid which was stirred in acetonitrile overnight, filtered and dried to afford 3-(1,3-benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (290 mg) as a solid; NMR Spectrum: (DMSOd6) 1.77 (dd, 1H), 1.82 (dd, 1H), 1.93-1.99 (m, 2H), 2.12 (bs, 1H), 2.32 (s, 3H), 2.58 (ddd, 1H), 3.01-3.07 (m, 2H), 4.06-4.25 (m, 1H), 7.41-7.48 (m, 2H), 7.64 (bs, 2H), 7.80 (dd, 1H), 7.84 (dd, 1H), 8.04 (s, 1H), 8.28 (d, 1H), 8.35 (d, 1H); Mass spectrum: M+H+: 375

Workup

  1. customThe mixture was evaporated to dryness
  2. additionthe residue was diluted in dichloromethane
  3. additionammonia in methanol 7N was added
  4. customAfter removal of solvents
  5. customthe crude product was purified by flash chromatography on silica gel eluting with 10% methanol in dichloromethane
  6. customThe solvent was evaporated to dryness
  7. customto afford a solid which
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-3a8112e9197f46398b657f7450d740f2
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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