1,2-Dichloroethane → HCID 178426411, compound

HRID 526649Notes

Reaction equation

HRID 526649 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[N:25][N:26]([C:29]3[CH:37]=[CH:36][C:32]([C:33]([OH:35])=O)=[CH:31][N:30]=3)[C:27]=2[OH:28])=[C:19]([CH3:38])[CH:18]=1)#[N:16].[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.C(#N)C>[OH:28][C:27]1[N:26]([C:29]2[CH:37]=[CH:36][C:32]([C:33]([N:43]3[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]3)=[O:35])=[CH:31][N:30]=2)[N:25]=[CH:24][C:23]=1[C:20]1[CH:21]=[CH:22][C:17]([C:15]#[N:16])=[CH:18][C:19]=1[CH3:38]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178426451HCID 178426451, compound

Product 1

HCID 178426411HCID 178426411, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

Combined EDC (599 mg, 3.12 mmol), HOBT (211 mg, 1.561 mmol) and 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (500 mg, 1.561 mmol) in DMF (10 ml) and added 1-methylpiperazine (519 μl, 4.68 mmol) and DIPEA (818 μl, 4.68 mmol) and the solution was stirred at 20° C. overnight. The reaction mixture was then purified by preparative HPLC (15-40% ACN in water under basic conditions) to give the free base, which was suspended in acetonitrile (28 mL) and treated with 1N aqueous hydrochloric acid (2.341 mL, 2.341 mmol). The resulting cloudy mixture was heated until cleared and allowed to cool to ambient temperature. The mixture was filtered and the filtrate was cooled to 0° C. and filtered again. The filtrate was diluted with ethyl ether (10 mL) to give a solid and the mixture was heated until all solids dissolved, and then cooled to ambient temperature to give a solid. The mixture was cooled to 0° C. and filtered, and the solid was dried in vacuum at 80° C. for 1 hour to give the title compound as a hydrochloride salt (94 mg, 13.7%) as a light pink solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3H) 2.79 (s, 3H) 3.16 (br. s., 4H) 3.64-4.57 (m, 4H) 7.67 (d, J=7.83 Hz, 1H) 7.74 (s, 1H) 7.78 (br. s., 1H) 8.12 (d, J=7.33 Hz, 1H) 8.21 (br. s., 1H) 8.51 (br. s., 1H) 8.57-8.61 (m, 1H); ESI-MS m/z (M+H)+ calc'd for C22H22N6O2, 403.18. found 403.2.

Workup

  1. customThe reaction mixture was then purified by preparative HPLC (15-40% ACN in water under basic conditions)
  2. customto give the free base, which
  3. temperatureThe resulting cloudy mixture was heated
  4. temperatureto cool to ambient temperature
  5. filtrationThe mixture was filtered
  6. temperaturethe filtrate was cooled to 0° C.
  7. filtrationfiltered again
  8. additionThe filtrate was diluted with ethyl ether (10 mL)
  9. customto give a solid
  10. temperaturethe mixture was heated until all solids
  11. dissolutiondissolved
  12. temperaturecooled to ambient temperature
  13. customto give a solid
  14. temperatureThe mixture was cooled to 0° C.
  15. filtrationfiltered
  16. customthe solid was dried in vacuum at 80° C. for 1 hour

Sources & evidence

ORD record
ord-337bd0d32de943f88e17f3bcf18bcfbc
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

Loading…