Piperidine → HCID 67319043, compound

HRID 244756Notes

Reaction equation

HRID 244756 reaction equation
Cl[CH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([NH:10][C:11]2[CH:19]=[C:18]([C:20]3[CH:28]=[C:27]([F:29])[CH:26]=[C:25]4[C:21]=3[CH:22]=[CH:23][NH:24]4)[CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][N:15]3S(C2C=CC=CC=2)(=O)=O)=[O:9])[N:7]=1.[NH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1>C(#N)C.O1CCOCC1.O>[F:29][C:27]1[CH:26]=[C:25]2[C:21]([CH:22]=[CH:23][NH:24]2)=[C:20]([C:18]2[CH:17]=[C:16]3[C:12]([CH:13]=[N:14][NH:15]3)=[C:11]([NH:10][C:8]([C:6]3[N:7]=[C:3]([CH2:2][N:39]4[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]4)[S:4][CH:5]=3)=[O:9])[CH:19]=2)[CH:28]=1

Participants

5

Reactant 2

HCID 8082Piperidine2×HCID 67029005HCID 67029005, compound

Product 1

HCID 67319043HCID 67319043, compoundYield 23.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 2-(chloromethyl)-N-[6-(6-fluoro-1H-indol-4-yl)-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg, 0.088 mmol) in acetonitrile (2 ml) was added piperidine (0.02 ml, 0.18 mmol) and the mixture was heated to 80° C. for 2 hours. Further piperidine (0.02 ml, 0.18 mmol) was added and heating was continued at 80° C. for 30 mins. The mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was taken up in MeOH and 2M aqueous NaOH (5 ml, 1:1, v.v) and stirred at room temperature for 1 hour, then neutralised with 2M aqueous HCl to ˜pH=5 and extracted with DCM (3×5 ml). The extracts were combined and the solvent removed under a stream of nitrogen. The residue was taken up again in MeOH and 2M aqueous NaOH (5 ml, 1:1, v/v) and stirred at room temperature for 3 hours. The mixture was neutralised with 2M aqueous HCl to ˜pH=7 and the MeOH was blown off under a stream of nitrogen. A precipitate was observed which was collected by filtration, then dissolved in 1 ml DMSO/MeOH (1:1) and purified by MDAP (Method B). The product-containing fractions were blown down under a stream of nitrogen to give a clear oil which was dissolved in dioxane/water (2 ml, 1:1, v/v) and freeze dried to give the title compound as a white solid (10 mg).

Workup

  1. temperatureheating
  2. temperatureThe mixture was cooled to room temperature
  3. customthe solvent was removed in vacuo
  4. extractionextracted with DCM (3×5 ml)
  5. customthe solvent removed under a stream of nitrogen
  6. stirring2M aqueous NaOH (5 ml, 1:1, v/v) and stirred at room temperature for 3 hours
  7. filtrationwas collected by filtration
  8. dissolutiondissolved in 1 ml DMSO/MeOH (1:1)
  9. custompurified by MDAP (Method B)
  10. customto give a clear oil which
  11. customv/v) and freeze dried

Sources & evidence

ORD record
ord-9549306cf5a4426eb0a2c0c0566677c6
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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