Hydrochloric Acid → HCID 178462759, compound

HRID 526654Notes

Reaction equation

HRID 526654 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2].N1(O)C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)C(C)C)C.Cl.Cl.[CH2:58]([N:60]1[CH2:65][CH2:64][NH:63][C@H:62]([CH3:66])[CH2:61]1)[CH3:59].Cl>O.C(O)C.CN(C=O)C>[CH2:58]([N:60]1[CH2:65][CH2:64][N:63]([C:19]([C:18]2[CH:22]=[CH:23][C:15]([N:12]3[C:13]([OH:14])=[C:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=4[CH3:24])[CH:10]=[N:11]3)=[N:16][CH:17]=2)=[O:20])[C@H:62]([CH3:66])[CH2:61]1)[CH3:59]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86767561HCID 86767561, compoundHCID 178426451HCID 178426451, compound

Product 1

HCID 178462759HCID 178462759, compoundYield 50.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 19096565Water ethanolSolvent

Procedure

Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (100 mg, 0.312 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (50.6 mg, 0.375 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (71.8 mg, 0.375 mmol), DMF (Volume: 624 μl), and N-ethyl-N-isopropylpropan-2-amine (273 μl, 1.561 mmol). The solution was stirred at ambient temperature for 5 minutes then (R)-1-ethyl-3-methylpiperazine dihydrochloride (69.1 mg, 0.343 mmol) was added. The reaction was stirred at ambient temperature for 12 h. The reaction was diluted with a pre-made solution of water:ethanol (1:1, 10 mL). The reaction was acidified to pH 5 using 1N HCl and left to stir slowly at ambient temperature overnight. The precipitate was filtered and the solids were washed with water:ethanol (1:1, 2 mL), then dried on the filter paper. The white solids were collected and dried further under vacuum. The dried solids were taken up in 10 volumes of water:ethanol (1:1) and stirred at reflux until the solution was almost completely translucent. The hot solution was filtered and then slowly cooled to ambient temperature and stirred slowly at ambient temperature overnight to give solids. The solids were filtered and washed with water:ethanol (1:1, 2 mL), partially dried on filter paper, then collected and dried under vacuum to give the title compound (67.7 mg, 0.157 mmol, 50.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01 (s, 3H) 1.21-1.37 (m, 3H) 1.92-2.06 (m, 1H) 2.09-2.21 (m, 1H) 2.42 (s, 5H) 2.67-2.99 (m, 2H) 3.05-4.61 (m, 3H) 7.61 (dd, J=8.08, 1.52 Hz, 1H) 7.68 (s, 1H) 7.86 (d, J=8.08 Hz, 1H) 8.00 (dd, J=8.59, 2.27 Hz, 1H) 8.08 (s, 1H) 8.40 (d, J=8.59 Hz, 1H) 8.49 (d, J=2.27 Hz, 1H). ESI-MS m/z [M+H]+ 431.3, ret time: 0.80 minutes.

Workup

  1. stirringThe reaction was stirred at ambient temperature for 12 h
  2. waitleft
  3. stirringto stir slowly at ambient temperature overnight
  4. filtrationThe precipitate was filtered
  5. washthe solids were washed with water:ethanol (1:1, 2 mL)
  6. customdried on the filter paper
  7. customThe white solids were collected
  8. customdried further under vacuum
  9. stirringstirred
  10. temperatureat reflux until the solution
  11. filtrationThe hot solution was filtered
  12. temperatureslowly cooled to ambient temperature
  13. stirringstirred slowly at ambient temperature overnight
  14. customto give solids
  15. filtrationThe solids were filtered
  16. washwashed with water:ethanol (1:1, 2 mL)
  17. custompartially dried
  18. filtrationon filter paper
  19. customcollected
  20. customdried under vacuum

Sources & evidence

ORD record
ord-d5405858ac0d44b4948c3d426b744753
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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