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

HRID 39450Notes

Reaction equation

HRID 39450 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-5f606f8959214b139bfb3c91eef1364d
Source dataset
uspto-grants-2013_09
Patent number
US08524910B2

Reaction notes

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