Dimethylformamide → 1-(benzo[d][1,3]dioxol-5-yl)-N-(pyridin-2-yl)cyclopropanecarboxamide

HRID 1516891Notes

Reaction equation

HRID 1516891 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([OH:15])=O)[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.S(Cl)(Cl)=O.CN(C)C=O.[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH2:31]>N1C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:31][C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=4)=[O:15])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 104392-AminopyridineHCID 24386Thionyl ChlorideHCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acid

Product 1

HCID 578951431-(benzo[d][1,3]dioxol-5-yl)-N-(pyridin-2-yl)cyclopropanecarboxamideYield 10.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

1-Benzo[1,3]dioxol-5-yl-cyclopropanecarboxylic acid (41 mg, 0.20 mmol) was placed in an oven-dried flask under nitrogen. Thionyl chloride (0.3 mL) and N,N-dimethylformamide (0.03 mL) were added and the solution was allowed to stir for 10 minutes at room temperature. The excess thionyl chloride was removed under vacuum and the resulting solid was suspended in anhydrous pyridine (1 mL). This solution was then slowly added to a solution of pyridin-2-amine (19 mg, 0.20 mmol) in anhydrous pyridine (1 mL). The resulting mixture was allowed to stir for 15 hours at 110° C. The crude product was then filtered, evaporated to dryness, dissolved in N,N-dimethylformamide (1 mL) and purified by reverse-phase preparative liquid chromatography utilizing a gradient of 0-99% acetonitrile in water containing 0.05% trifluoroacetic acid to yield the pure product (5.9 mg, 0.021 mmol, 10%). ESI-MS m/z calc. 282.1, found 283.1 (M+1)+. Retention time 2.13 minutes.

Workup

  1. customThe excess thionyl chloride was removed under vacuum
  2. stirringto stir for 15 hours at 110° C
  3. filtrationThe crude product was then filtered
  4. customevaporated to dryness
  5. dissolutiondissolved in N,N-dimethylformamide (1 mL)
  6. custompurified by reverse-phase preparative liquid chromatography

Sources & evidence

ORD record
ord-fe7b18f8619047dd9f1e72dcf8bde6e0
Source dataset
uspto-grants-2012_07
Patent number
US08227615B2

Reaction notes

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