Dimethylformamide → 1-(Benzo[d][1,3]dioxol-6-yl)-N-(6-bromopyridin-2-yl)cyclopropanecarboxamide

HRID 17951

Reaction equation

HRID 17951 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.[Br:25][C:26]1[N:31]=[C:30]([NH2:32])[CH:29]=[CH:28][CH:27]=1>N1C=CC=CC=1>[O:3]1[C:4]2[CH:9]=[C:8]([C:10]3([C:13]([NH:32][C:30]4[CH:29]=[CH:28][CH:27]=[C:26]([Br:25])[N:31]=4)=[O:15])[CH2:11][CH2:12]3)[CH:7]=[CH:6][C:5]=2[O:1][CH2:2]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 3008092-Amino-6-bromopyridineHCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acid

Product 1

HCID 591658951-(Benzo[d][1,3]dioxol-6-yl)-N-(6-bromopyridin-2-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
60 °C

Procedure

(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarboxylic acid (1.2 g, 5.8 mmol) was placed in an oven-dried flask under nitrogen. Thionyl chloride (2.5 mL) and N,N-dimethylformamide (0.3 mL) were added and the solution was allowed to stir at 60° C. for 30 minutes. The excess thionyl chloride was removed under vacuum and the resulting solid was suspended in 5 mL of anhydrous pyridine. This solution was then slowly added to a solution of 6-bromopyridin-2-amine (1.0 g, 5.8 mmol) suspended in 10 mL of anhydrous pyridine. The resulting mixture was allowed to stir for 15 hours at 110° C. The mixture was then evaporated to dryness, suspended in 50 mL of dichloromethane, and washed with three 20 mL portions of 1N NaOH. The organic layer was dried over sodium sulfate, evaporated to near dryness, and then purified by silica gel column chromatography utilizing dichloromethane containing 2.5% triethylamine as the eluent to yield the pure product. ESI-MS m/z calc. 361.2. found 362.1 (M+1)+; Retention time 3.43 minutes. 1H NMR (400 MHz, DMSO-d6) δ 1.10-1.17 (m, 2H), 1.42-1.55 (m, 2H), 6.06 (s, 2H), 6.92-7.02 (m, 2H), 7.09 (d, J=1.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 7.73 (t, J=8.0 Hz, 1H), 8.04 (d, J=8.2 Hz, 1H), 8.78 (s, 1H).

Workup

  1. customThe excess thionyl chloride was removed under vacuum
  2. stirringto stir for 15 hours at 110° C
  3. customThe mixture was then evaporated to dryness
  4. washwashed with three 20 mL portions of 1N NaOH
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customevaporated
  7. custompurified by silica gel column chromatography
  8. customto yield the pure product

Sources & evidence

ORD record
ord-bc91f57506f04df495894f26f8f86c46
Source dataset
uspto-grants-2010_06
Patent number
US07741321B2

Linked notes

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