Hydrochloric Acid → HCID 21106440, compound

HRID 1817118Notes

Reaction equation

HRID 1817118 reaction equation
[C:1]([N:4]1[CH:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:16]=[C:15]([N:17]3[CH:21]=[N:20][C:19]([NH:22][C:23]4[CH:31]=[CH:30][C:26](C(O)=O)=[CH:25][CH:24]=4)=[N:18]3)[CH:14]=[CH:13][N:12]=2)[CH2:6][CH:5]1[CH3:32])(=[O:3])[CH3:2].CC[N:35](C(C)C)C(C)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C(O)(C(F)(F)F)=O.Cl>CN1C(=O)CCC1.CO>[NH2:35][C:26]1[CH:30]=[CH:31][C:23]([NH:22][C:19]2[N:20]=[CH:21][N:17]([C:15]3[CH:14]=[CH:13][N:12]=[C:11]([N:7]4[CH2:6][CH:5]([CH3:32])[N:4]([C:1](=[O:3])[CH3:2])[CH:9]([CH3:10])[CH2:8]4)[CH:16]=3)[N:18]=2)=[CH:24][CH:25]=1

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 68419598HCID 68419598, compound

Product 1

HCID 21106440HCID 21106440, compoundYield 33.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 8 g of 4-{1-[2-(4-Acetyl-3,5-dimethyl-piperazin-1-yl)-pyridin-4-yl]-1H-[1,2,4]triazol-3-ylamino}-benzoic acid (18.3 mMol, 1.00 equiv) in 150 mL of NMP was added 9 mL of Hunig's base followed by 6 g of DPPA (21.8 mMol, 1.19 equiv). The reaction was stirred for 30 min at 25° C. To the reaction mixture was then added 200 mL of TFA and the resulting solution was warmed to 90° C. for 12 hr. After cooling to 25° C., the reaction was quenched with 200 mL of concentrated ammonium hydroxide and concentrated. The resulting oil was triturated with CH2Cl2 and the solid was isolated by filtration. The solid was then dissolved in MeOH (100 mL) and concentrated to 50 mL. The resulting precipitate was isolated and treated with 50 mL of 1 N HCl and concentrated via rotary evaporation. The oil was triturated with ethanol and the resulting solid was removed by filtration. The ethanol solution was concentrated to give 2.5 g of 1-(4-{4-[3-(4-Amino-phenylamino)-[1,2,4]triazol-1-yl]-pyridin-2-yl}-2,6-dimethyl-piperazin-1-yl)-ethanone (6.15 mMol, 33.6% yield) as the HCl salt. 1H NMR (500 MHz, CDCl3) ∂ 8.39 (1H, s), 8.10 (1H, d), 7.22 (2H, d), 7.15 (2H, d), 6.95 (1H, s), 6.92 (2H, m), 6.75 (1H, m), 6.65 (2H, d), 4.15 (2H, m), 3.08 (2H, m), 2.99 (2H, m), 2.10 (3H, s), 1.30 (6H, m) ppm. LC/MS: 0.54 min/407.3 (M+1)

Workup

  1. temperaturethe resulting solution was warmed to 90° C. for 12 hr
  2. temperatureAfter cooling to 25° C.
  3. customthe reaction was quenched with 200 mL of concentrated ammonium hydroxide
  4. concentrationconcentrated
  5. customThe resulting oil was triturated with CH2Cl2
  6. customthe solid was isolated by filtration
  7. concentrationconcentrated to 50 mL
  8. customThe resulting precipitate was isolated
  9. concentrationconcentrated via rotary evaporation
  10. customThe oil was triturated with ethanol
  11. customthe resulting solid was removed by filtration
  12. concentrationThe ethanol solution was concentrated

Sources & evidence

ORD record
ord-1607bb6c83e54de3915b45b5326f0038
Source dataset
uspto-grants-2009_10
Patent number
US07598245B2

Reaction notes

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