Water → HCID 178511846, compound

HRID 867718Notes

Reaction equation

HRID 867718 reaction equation
[N:1]#[C:2]Br.C(=O)(O)[O-].[Na+].[Cl:9][C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[N:15][NH:16]2)=[CH:12][CH:11]=1.O>CS(C)=O>[Cl:9][C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:19]3[CH2:24][CH2:23][N:22]([C:2]#[N:1])[CH2:21][CH2:20]3)=[N:15][NH:16]2)=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 178477868HCID 178477868, compound

Product 1

HCID 178511846HCID 178511846, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

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. customThe resulting solid was collected
  2. customdried
  3. customRecrystallization from toluene-hexane

Sources & evidence

ORD record
ord-6fc4281542b746fb840df23a7421ef0e
Source dataset
uspto-grants-1988_10
Patent number
US04775761

Reaction notes

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