Nitrogen → 8-(oxazol-2-yl)-2-(2-(quinolin-2-yl)ethyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 1777782Notes

Reaction equation

HRID 1777782 reaction equation
Br[C:2]1[C:3]2[N:4]([C:8](=[O:23])[N:9]([CH2:11][CH2:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.N#N.C([Sn](CCCC)(CCCC)[C:31]1[O:32][CH:33]=[CH:34][N:35]=1)CCC>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:32]1[CH:33]=[CH:34][N:35]=[C:31]1[C:2]1[C:3]2[N:4]([C:8](=[O:23])[N:9]([CH2:11][CH2:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 947NitrogenHCID 154861832-(Tri-n-butylstannyl)oxazole2×HCID 715733828-bromo-2-(2-(quinolin-2-yl)ethyl)-[1,2,4]triazolo[4,3-a]pridin-3(2H)-one

Product 1

HCID 715733858-(oxazol-2-yl)-2-(2-(quinolin-2-yl)ethyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 16.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
125 °C

Procedure

A solution of bromide 1-6 (43 mg, 0.116 mmol) in THF (2 mL) in a microwave vial was sparged with N2 gas for 5 min, and 2-(tributylstannyl)oxazole (83 mg, 0.233 mmol) and tetrakis(triphenylphosphine)palladium (13 mg, 0.012 mmol) were added. The vial was capped and heated at 125° C. under microwave irradiation for 20 min, then another 30 min at 130° C. An additional portion of 2-(tributylstannyl)oxazole (50 mg, 0.140 mmol) was added, and the vial was heated at 85° C. in an oil bath for 16 h. After cooling, the reaction mixture was directly purified by silica gel flash column chromatography (12 g cartridge), eluting with 40-100% EtOAc/hexanes then 2% EtOH/EtOAc. The fractions containing the desired product (4-1) were pooled, and after solvent removal in vacuo, 6.8 mg (16%) of a yellow solid were obtained. 1H NMR (300 MHz, CHCl3-d): δ 8.07 (d, J=8.4 Hz, 1H), 8.02 (d, J=7.8 Hz, 1H), 7.92 (dd, J=6.9, 1.2 Hz, 1H), 7.88 (dd, 6.9, 1.2 Hz, 1H), 7.80 (d, J=0.6 Hz, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.68 (ddd, J=8.4, 7.2, 1.5 Hz, 1H), 7.50 (ddd, Jr=7.8, 6.6, 1.2 Hz, 1H), 7.35 (s, 1H), 7.33 (s, 1H), 6.64 (t, J=7.2 Hz, 1H), 4.69 (t, J=7.5 Hz, 2H), 3.61 (t, J=7.5 Hz, 2H). HRMS (ES) 358.1299 (M+H) found, 358.1302 required.

Workup

  1. customThe vial was capped
  2. customanother 30 min
  3. customat 130° C
  4. temperaturethe vial was heated at 85° C. in an oil bath for 16 h
  5. temperatureAfter cooling
  6. customthe reaction mixture was directly purified by silica gel flash column chromatography (12 g cartridge)
  7. washeluting with 40-100% EtOAc/hexanes
  8. additionThe fractions containing the desired product (4-1)
  9. customafter solvent removal in vacuo

Sources & evidence

ORD record
ord-e445687d172e45f7bcdce60a15d8d803
Source dataset
uspto-grants-2016_02
Patent number
US09266881B2

Reaction notes

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