N-Hydroxyacetamidine → 7-{5-[1-(3-Methyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl}-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline

HRID 1521607Notes

Reaction equation

HRID 1521607 reaction equation
[CH:1]1[N:5]2[C:6]3[C:11]([CH2:12][CH2:13][C:4]2=[N:3][N:2]=1)=[CH:10][C:9]([C:14]1[CH:15]=[C:16]([C:20]2([C:23](OC)=[O:24])[CH2:22][CH2:21]2)[CH:17]=[N:18][CH:19]=1)=[CH:8][CH:7]=3.[C:27](=[N:30]O)([NH2:29])[CH3:28].[O-]CC.[Na+]>C(O)C>[CH3:28][C:27]1[N:30]=[C:23]([C:20]2([C:16]3[CH:15]=[C:14]([C:9]4[CH:10]=[C:11]5[C:6](=[CH:7][CH:8]=4)[N:5]4[CH:1]=[N:2][N:3]=[C:4]4[CH2:13][CH2:12]5)[CH:19]=[N:18][CH:17]=3)[CH2:21][CH2:22]2)[O:24][N:29]=1

Participants

5

Reactant 3

HCID 30926N-HydroxyacetamidineHCID 2723922Sodium ethoxideHCID 66576768HCID 66576768, compound

Product 1

HCID 899616127-{5-[1-(3-Methyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl}-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

To a vial containing the title compound from Example 71 Step D (75 mg, 0.217 mmol), acetamide oxime (32.1 mg, 0.433 mmol) and sodium ethoxide (73.7 mg, 1.083 mmol) was added ethanol (2.2 mL). The vial was capped tightly and heated to 150° C. for 15 minutes in the microwave. The reaction solution was then concentrated under reduced pressure. The resulting material was diluted with acetonitrile and then purified by HPLC (C18 column, 10 to 100% acetonitrile/water, both 0.1% v/v trifluoroacetic acid). Fractions containing product were combined, aqueous 1 N HCl solution was added, and the resulting solution concentrated to provide the title compound: LCMS m/z 370.97 [M+H]+; 1H NMR (500 MHz, CD3OD) δ 10.1 (s, 1H), 9.28 (s, 1H), 9.13 (s, 1H), 8.1-8.01 (m, 4H), 3.49-3.46 (m, 2H), 3.39-3.36 (m, 2H), 2.29 (s, 3H), 2.04-2.02 (m, 2H), 1.94-1.91 (m, 2H).

Workup

  1. customThe vial was capped tightly
  2. concentrationThe reaction solution was then concentrated under reduced pressure
  3. additionThe resulting material was diluted with acetonitrile
  4. custompurified by HPLC (C18 column, 10 to 100% acetonitrile/water
  5. additionFractions containing product
  6. additionaqueous 1 N HCl solution was added
  7. concentrationthe resulting solution concentrated

Sources & evidence

ORD record
ord-97ec545b8c3d4b05be62b2f1fb441828
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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