Piperidine → N-[5-(3,5-difluoro-benzyloxy)-1H-indazol-3-yl]-3-piperidin-1-ylmethyl-benzamide

HRID 1803854Notes

Reaction equation

HRID 1803854 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[C:6]([NH:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH2:19][C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)[CH:16]=2)[NH:11][N:10]=1)=[O:7].CCN(C(C)C)C(C)C.[NH:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>C(O)C.O>[F:26][C:24]1[CH:25]=[C:20]([CH:21]=[C:22]([F:27])[CH:23]=1)[CH2:19][O:18][C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[NH:8][C:6](=[O:7])[C:5]1[CH:28]=[CH:29][CH:30]=[C:3]([CH2:2][N:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[CH:4]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 462448313-chloromethyl-N-[5-(3,5-difluoro-benzyloxy)-1H-indazol-3-yl]-benzamide

Product 1

HCID 46244833N-[5-(3,5-difluoro-benzyloxy)-1H-indazol-3-yl]-3-piperidin-1-ylmethyl-benzamideYield 66.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

3-Chloromethyl-N-[5-(3,5-difluoro-benzyloxy)-1H-indazol-3-yl]-benzamide (100 mg, 0.2342 mmol) in absolute ethanol (2.5 mL) was treated with DIPEA (0.12 mL, 0.7026 mmol) and piperidine (0.069 mL, 0.7026 mmol) and heated to reflux temperature. After 1 hour the reaction mixture was diluted with water, filtered with suction and dried at 50° C. under vacuum. Purification by flash chromatography over silica gel (eluent: DCM:MeOH:7N NH3 in MeOH 95:5:0.5) afforded 74 mg of title compound in 66% yield.

Workup

  1. temperatureheated
  2. temperatureto reflux temperature
  3. filtrationfiltered with suction
  4. customdried at 50° C. under vacuum
  5. customPurification by flash chromatography over silica gel (eluent: DCM:MeOH:7N NH3 in MeOH 95:5:0.5)

Sources & evidence

ORD record
ord-fd4dbaca847d4ed6813b40e60eb6bb17
Source dataset
uspto-grants-2013_01
Patent number
US08354399B2

Reaction notes

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