HCID 86724908, compound → 1428862-32-1

HRID 1523733Notes

Reaction equation

HRID 1523733 reaction equation
[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([NH:15][NH2:16])=[O:14])=[N:5]1)([CH3:3])[CH3:2].Cl.[CH3:18][O:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH:26]([C:29](O)=O)[CH2:25][CH2:24]1>P(Cl)(Cl)(Cl)=O>[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]2[O:14][C:29]([CH:26]3[CH2:25][CH2:24][N:23]([CH2:22][CH2:21][CH2:20][O:19][CH3:18])[CH2:28][CH2:27]3)=[N:16][N:15]=2)=[N:5]1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 86724908HCID 86724908, compoundHCID 86724918HCID 86724918, compound

Product 1

HCID 715082911428862-32-1Yield 59.8%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
0 °C

Procedure

To the mixture of 1-isopropyl-1H-indazole-3-carboxylic acid hydrazide (15.0 grams, 68.8 mmol) and 1-(3-Methoxy propyl)-piperidine-4-carboxylic acid hydrochloride (20.9 grams, 88.2 mmol, obtained in preparation 7) cooled at 0° C. was added phosphoryl chloride (130 mL). The reaction temperature was gradually raised to 100° C. and stirred was 2 hours. Upon completion of the reaction, it was cooled to 0° C. and triturated with hexanes (3×250 mL). The crude product was basified with aqueous sodium hydroxide solution and extracted with 5% methanol in dichloromethane. The combined organic layer was dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to obtain 1-isopropyl-3-{5-[1-(3-methoxy propyl)piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole (15.78 grams)

Workup

  1. temperatureThe reaction temperature was gradually raised to 100° C.
  2. customUpon completion of the reaction, it
  3. temperaturewas cooled to 0° C.
  4. customtriturated with hexanes (3×250 mL)
  5. extractionextracted with 5% methanol in dichloromethane
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulphate
  7. customthe solvent was removed under reduced pressure
  8. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d06447fddae34f92b84b2de8d1c9991e
Source dataset
uspto-grants-2015_07
Patent number
US09079894B2

Reaction notes

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