Sodium Methoxide → HCID 178496814, compound

HRID 845646Notes

Reaction equation

HRID 845646 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]#[N:18])[CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[CH3:19][O-:20].[Na+]>CO>[CH3:19][O:20][C:17]([N:14]1[CH2:13][CH2:12][CH:11]([C:6]2[C:5]3[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=3)[NH:8][N:7]=2)[CH2:16][CH2:15]1)=[NH:18]

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 178511846HCID 178511846, compound

Product 1

HCID 178496814HCID 178496814, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a stirred mixture of cyanogen bromide (1.8 g, 0.017 mol), sodium bicarbonate (2.80 g) and dimethyl sulfoxide (DMSO) (40 ml) was added dropwise 6-chloro-3-(4-piperidinyl)-1H-indazole (4.0 g, 0.017 mol) of Example 52 dissolved in DMSO (50 ml). The reaction was stirred at ambient temperature for 1 hour and poured into water. The resulting solid was collected, dried and weighed 4.0 g. Recrystallization from toluene-hexane afforded 3.1 g (70%) of 4-(6-chloro-1H-indazol-3-yl)piperidine-1-carbonitrile, m.p. 180°-188° C. To a stirred mixture of 4-(6-chloro-1H-indazol-3-yl)-piperidine 1-carbonitrile (3.0 g., 0.015 mol) in methanol (30 ml) was added a solution of 25% sodium methoxide in methanol (2.5 ml). The reaction was warmed on a steam bath to effect solution and then stirred at ambient temperature for 16 hours. Most of the methanol was removed in vacuo and the residue was diluted with water. An initial oil solidified and 3.5 g of a solid was collected. This was recrystallized from methanol-water to yield 2.9 g (66%) of 4-(6-chloro-1H-indazol-3-yl)piperidine-1-carboximidic acid methyl ester, mp 173°-175° C.

Workup

  1. temperatureThe reaction was warmed on a steam bath
  2. customMost of the methanol was removed in vacuo
  3. additionthe residue was diluted with water
  4. custom3.5 g of a solid was collected
  5. customThis was recrystallized from methanol-water

Sources & evidence

ORD record
ord-f32adc05af54496f8f091b115772885e
Source dataset
uspto-grants-1988_07
Patent number
US04758668

Reaction notes

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