Sodium Methoxide → HCID 178496814, compound

HRID 652176Notes

Reaction equation

HRID 652176 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-0c479d594ae2414fa56cc5353209d298
Source dataset
uspto-grants-1987_06
Patent number
US04670447

Reaction notes

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