Pyridine → HCID 76684688, compound

HRID 1752807Notes

Reaction equation

HRID 1752807 reaction equation
[CH3:1][CH2:2][C:3](=O)[CH2:4][C:5](=O)[CH2:6][CH3:7].[NH2:10][C:11]1[NH:15][N:14]=[C:13]([CH2:16][CH2:17][CH2:18][N:19]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:20][CH2:21][OH:22])[N:12]=1.N1C=CC=CC=1>C(Cl)(Cl)Cl.CO.C(O)(=O)C>[CH2:2]([C:3]1[CH:4]=[C:5]([CH2:6][CH3:7])[N:15]2[N:14]=[C:13]([CH2:16][CH2:17][CH2:18][N:19]([C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)[CH2:20][CH2:21][OH:22])[N:12]=[C:11]2[N:10]=1)[CH3:1]

Participants

5

Reactant 3

HCID 1049PyridineHCID 819233,5-Heptanedione2×HCID 178508400HCID 178508400, compound

Product 1

HCID 76684688HCID 76684688, compoundYield 72.1%

Reagents, catalysts & solvents 1

HCID 21866353chloroform methanol HOAcSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 3,5-heptanedione (216 mg, 1.68 mmol), 2-{[3-(5-amino-1H-1,2,4-triazol-3-yl)propyl](4-fluorophenyl)amino}ethan-1-ol (470 mg, 1.68 mmol), and pyridine (3 mL) was added to a 50 mL RBF with a magnetic stirring bar. The flask was fitted with a condenser, and warmed in an oil bath to a gentle reflux at 125° C. Progress of the reaction was monitored by TLC using chloroform:methanol:acetic acid (9:1:0.2) (Rf starting material=0.1, Rf product=0.7). The solution was heated for 17 hours, and an additional portion of 3,5-heptanedione (95 mg, 0.74 mmol) was added. After an additional 6 hours of heating, the reaction was complete by TLC disappearance of the starting material. The mixture was allowed to cool to room temperature, concentrated under reduced pressure, and the crude material was purified by silica gel column chromatography using a gradient elution of 65-100% ethyl acetate in hexanes to afford the title compound as an oil (450 mg, 72% yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.11 (s, 1H), 6.95 (m, 2H), 6.70 (m, 2H), 4.66 (t, 1H), 3.50 (q, 2H), 3.40 (t, 2H), 3.35 (m, 2H), 3.09 (q, 2H), 2.86 (q, 4H), 1.99 (m, 2H), 1.34 (t, 3H), 1.28 (t, 3H). EM (calc.): 371.2; MS (ESI) m/e: 372.3 (M+H)+.

Workup

  1. additionwas added to a 50 mL RBF with a magnetic stirring bar
  2. customThe flask was fitted with a condenser
  3. temperaturewarmed in an oil bath to
  4. temperatureThe solution was heated for 17 hours
  5. temperatureAfter an additional 6 hours of heating
  6. temperatureto cool to room temperature
  7. concentrationconcentrated under reduced pressure
  8. customthe crude material was purified by silica gel column chromatography
  9. washa gradient elution of 65-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-60e9acfe2cda42eaafc75b59feb60f96
Source dataset
uspto-grants-2015_10
Patent number
US09163027B2

Reaction notes

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