Hydrochloric Acid → HCID 19020633, compound

HRID 1109457Notes

Reaction equation

HRID 1109457 reaction equation
C([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[N:11]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:12]=[C:13]3[C:18]=2[CH:17]=[CH:16][C:15]([F:19])=[CH:14]3)[CH2:6][CH2:5]1)(=O)C.[ClH:27]>>[ClH:27].[F:19][C:15]1[CH:16]=[CH:17][C:18]2[C:13]([CH:14]=1)=[N:12][N:11]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:10]=2[CH:7]1[CH2:8][CH2:9][NH:4][CH2:5][CH2:6]1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 19020637HCID 19020637, compound

Product 1

HCID 19020633HCID 19020633, compoundYield 25.1%

Procedure

To a stirred mixture of 15.8 parts of a sodium hydride dispersion 50% and 660 parts of dimethyl sulfoxide were added portionwise 78.4 parts of 1-acetyl-4-(6-fluoro-2H-indazol-3-yl)piperidine under nitrogen atmosphere. Upon complete addition, stirring was continued for 1 hour at room temperature. 42 Parts of chloromethylbenzene were added dropwise during 45 minutes. Upon completion, stirring was continued overnight at room temperature. The reaction mixture was poured into crushed ice and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography (HPLC) over silica gel using a mixture of methylbenzene and methanol (90:10 by volume) as eluent. The first fraction was collected and the eluent was evaporated, yielding 91 parts (86.3%) of 1-acetyl-4-[6-fluoro-2-(phenylmethyl)-2H-indazol-3-yl]piperidine as a residue (int. 1). b) A mixture of 8 parts of 1-acetyl-4-[6-fluoro-2-(phenylmethyl)-2H-indazol-3-yl] piperdine and 70 parts of a hydrochloric acid solution 6N was stirred for 6 hours at reflux temperature. The reaction mixture was evaporated and the oily residue was crystallized from 2-propanol. The product was filtered off and dried, yielding 2 parts (25.1%) of 6-fluoro-2-(phenylmethyl)-3-(4-piperidinyl)-2H-indazole monohydrochloride; mp.>300° C. (int. 2).

Workup

  1. temperatureat reflux temperature
  2. customThe reaction mixture was evaporated
  3. customthe oily residue was crystallized from 2-propanol
  4. filtrationThe product was filtered off
  5. customdried

Sources & evidence

ORD record
ord-50d932b4f5274815b249f3ae5760c5e5
Source dataset
uspto-grants-1994_06
Patent number
US05321028

Reaction notes

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