Hydrochloric Acid → HCID 73505856, compound

HRID 590877Notes

Reaction equation

HRID 590877 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[N:5]=[C:4]([NH:11][C:12]([NH:14][C@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])=[O:13])[CH:3]=1.[NH2:23][NH2:24].Cl.C(=O)(O)[O-].[Na+]>C(O)C>[NH2:9][C:8]1[C:7]2[C:6]([CH3:10])=[N:5][C:4]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:3][C:2]=2[NH:24][N:23]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9321HydrazineHCID 516892Sodium BicarbonateHCID 118380940HCID 118380940, compound

Product 1

HCID 73505856HCID 73505856, compoundYield 41.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
95 °C

Procedure

A flask was charged with (S) -1-(4-chloro-5-cyano-6-methylpyridin-2-yl)-3-(1-phenylethyl)urea (920 mg) and ethanol (6989 μl) and hydrazine (183 μl) was added. The reaction was heated to 95° C. for 17 hours. LC/MS showed the reaction was mostly but not entirely complete (˜15% remaining starting material by LC/MS integration). The reaction was heated for 5 additional hours. After cooling, HCl (1N, 14.6 mL) was added and the reaction was stirred for 30 minutes. The reaction was poured into a 500 mL separatory funnel containing 150 mL of concentrated sodium bicarbonate solution. The resulting emulsion was washed 3× with chloroform/IPA (4:1, 100 mL portions). The combined organic washings were dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (0-10% EtOAc/MeOH+0.1% ammonia) was performed and the active fractions were concentrated to dryness yielding the title compound as a white solid (400 mg, 41.1%). MS ESI calc'd for C16H18N6O [M+H]+ 311. found 311. 1H NMR (ppm500 Mhz, DMSO-d6): δ 9.30 (s, 1H), 8.74 (d, J=0.9 Hz, 1H), 8.29 (s, 1H), 8.07 (s, 1H), 7.37-7.32 (m, 5H), 7.28-7.21 (m, 1H), 6.60 (s, 2H), 4.88 (p, J=7.0 Hz), 2.47 (s, 3H), 1.42 (d, J=6.9 Hz, 3H).

Workup

  1. additionwas added
  2. temperatureThe reaction was heated for 5 additional hours
  3. temperatureAfter cooling
  4. additionThe reaction was poured into a 500 mL separatory funnel
  5. washThe resulting emulsion was washed 3× with chloroform/IPA (4:1, 100 mL portions)
  6. dry with materialThe combined organic washings were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. concentrationthe active fractions were concentrated to dryness

Sources & evidence

ORD record
ord-0d660a01dac0470ab218a817af70483a
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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