Phosphorus oxychloride → HCID 71534484, compound

HRID 1523734Notes

Reaction equation

HRID 1523734 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.[CH:18]1([N:22]2[CH2:27][CH2:26][CH:25]([CH2:28][C:29](O)=O)[CH2:24][CH2:23]2)[CH2:21][CH2:20][CH2:19]1.P(Cl)(Cl)(Cl)=O>>[CH:18]1([N:22]2[CH2:23][CH2:24][CH:25]([CH2:28][C:29]3[O:14][C:13]([C:6]4[C:7]5[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=5)[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=4)=[N:15][N:16]=3)[CH2:26][CH2:27]2)[CH2:19][CH2:20][CH2:21]1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 86724908HCID 86724908, compoundHCID 86724919HCID 86724919, compound

Product 1

HCID 71534484HCID 71534484, compoundYield 30%

Conditions

Temperature
0 °C

Procedure

To the mixture of 1-isopropyl-1H-indazole-3-carboxylic acid hydrazide (120 mg, 0.55 mmol) and (1-cyclobutyl piperidin-4-yl) acetic acid hydrochloride (147 mg, 0.74 mmol, obtained in preparation 6) cooled at 0° C., was added phosphoryl chloride (1.5 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 (3×25 mL). The crude product was cooled to 0° C., 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 3-[5-(1-cyclobutyl piperidin-4-yl methyl)-[1,3,4]oxadiazol-2-yl]-1-isopropyl-1H-indazole (62 mg)

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 (3×25 mL)
  5. temperatureThe crude product was cooled to 0° C.
  6. extractionextracted with 5% methanol in dichloromethane
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulphate
  8. customthe solvent was removed under reduced pressure
  9. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8a8c841d850245b3a9871b4159ef359a
Source dataset
uspto-grants-2015_07
Patent number
US09079894B2

Reaction notes

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