Hydrochloric Acid → HCID 135979621, compound

HRID 1784018Notes

Reaction equation

HRID 1784018 reaction equation
C(OC([N:8]([C:18]1[C:19]2[N:20]([N:29]=[CH:30][N:31]=2)[C:21]([C:24]2[CH:25]=[N:26][NH:27][CH:28]=2)=[CH:22][N:23]=1)[C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12](O)=[O:13])=O)(C)(C)C.[CH2:32]([NH2:34])[CH3:33].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.CO.CCO.C(N(CC)CC)C>[CH2:32]([NH:34][C:12](=[O:13])[C:11]1[CH:15]=[CH:16][CH:17]=[C:9]([NH:8][C:18]2[C:19]3[N:20]([N:29]=[CH:30][N:31]=3)[C:21]([C:24]3[CH:28]=[N:27][NH:26][CH:25]=3)=[CH:22][N:23]=2)[CH:10]=1)[CH3:33]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 6341EthylamineHCID 2724699PyBOPHCID 135979611HCID 135979611, compound

Product 1

HCID 135979621HCID 135979621, compoundYield 20.1%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent2×

Procedure

3-{tert-Butoxycarbonyl-[5-(1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]-amino}benzoic acid (42 mg, 0.10 mmol), ethylamine (12 M aq., 42 μL, 0.50 mmol), and triethylamine (28 μL, 0.20 mmol) are stirred in DMF (0.30 mL) and PyBOP (57 mg, 0.11 mmol) is added. Stirring is continued overnight. The reaction mixture is partitioned between EtOAc (7 mL) and NaHCO3 (sat. aq., 7 mL) and the layers are separated. The combined organic layers are washed with brine (2×5 mL) and dried over Na2SO4. Evaporation of the solvent affords an oil which is dissolved in MeOH (0.3 mL) containing HCl (12 M aq., 0.15 mL) and stirred overnight. Triethylamine (0.25 mL) and EtOH (2 mL) are added and the solvents removed under reduced pressure. The residue is purified by preparative HPLC to afford the title compound as a white solid (7 mg). 1H NMR (DMSO-d6, 400 MHz): δ=13.29 ppm (s, 0.8H); 10.01 (s, 0.9H); 8.77 (s, 1.0H); 8.65 (s, 1.0H); 8.52 (s, 1.1H); 8.41-8.37 (m, 2.1H); 8.25 (s, 1.0H); 8.08 (d, 1.0H); 7.47 (d, 1.0H); 7.41 (t, 1.1H); 7.04-7.03 (m, 0.5H); 3.32 (s, 29.2H (water)); 1.14 (t, 3.5H). LCMS: Rt=0.95 min (100%), m/z (ESI) 349 (M+H)+.

Workup

  1. customThe reaction mixture is partitioned between EtOAc (7 mL) and NaHCO3 (sat. aq., 7 mL)
  2. customthe layers are separated
  3. washThe combined organic layers are washed with brine (2×5 mL)
  4. dry with materialdried over Na2SO4
  5. customEvaporation of the solvent
  6. customaffords an oil which
  7. stirringstirred overnight
  8. customthe solvents removed under reduced pressure
  9. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-828742442cf1402b967da9c94c959a02
Source dataset
uspto-grants-2009_03
Patent number
US07501411B2

Reaction notes

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