Acetic Acid → HCID 86719324, compound

HRID 1752808Notes

Reaction equation

HRID 1752808 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.[OH-].[Na+].[C:32](O)(=[O:34])[CH3:33]>>[C:32]([O:22][CH2:21][CH2:20][N:19]([CH2:18][CH2:17][CH2:16][C:13]1[N:12]=[C:11]2[N:10]=[C:5]([CH2:6][CH3:7])[CH:4]=[C:3]([CH2:2][CH3:1])[N:15]2[N:14]=1)[C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)(=[O:34])[CH3:33]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 819233,5-HeptanedioneHCID 178508400HCID 178508400, compound

Product 1

HCID 86719324HCID 86719324, compound

Conditions

Temperature
135 °C

Procedure

A mixture of 3,5-heptanedione (18.8 mg, 0.147 mmol), 2-{[3-(5-amino-1H-1,2,4-triazol-3-yl)propyl](4-fluorophenyl)amino}ethan-1-ol (50 mg, 0.179 mmol), and glacial acetic acid (1 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 135° C. for 18 h. Progress of the reaction was monitored by analytical HPLC with UV detection (Rt=5.5 min). The mixture was added to stirring ice/water (15 mL), and the pH was adjusted to basic with 1 N sodium hydroxide. The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography using a gradient elution of 65-100% ethyl acetate in hexanes. The material was concentrated under reduced pressure and the title compound was obtained (20 mg, 37%). EM (calc.): 413.2; MS (ESI) m/e: 414.2 (M+H)+. 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.11 (s, 1H), 6.97 (m, 2H), 6.75 (m, 2H), 4.12 (t, 2H), 3.54 (t, 2H), 3.40 (t, 2H), 3.10 (q, 2H), 2.88 (m, 4H), 1.99 (m, 2H), 1.95 (s, 3H), 1.35 (t, 3H), 1.28 (t, 3H).

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. additionThe mixture was added
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by silica gel chromatography
  10. washa gradient elution of 65-100% ethyl acetate in hexanes
  11. concentrationThe material was concentrated under reduced pressure

Sources & evidence

ORD record
ord-80f66516303640c1ab7320b14779bb82
Source dataset
uspto-grants-2015_10
Patent number
US09163027B2

Reaction notes

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