Triethylamine → 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromo-6-methylpyridin-3-yl)cyclopropanecarboxamide

HRID 2401918Notes

Reaction equation

HRID 2401918 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.[Br:20][C:21]1[CH:22]=[C:23]([NH2:28])[CH:24]=[N:25][C:26]=1[CH3:27].C(N(CC)CC)C>ClCCl.CN(C)C=O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:28][C:23]4[CH:24]=[N:25][C:26]([CH3:27])=[C:21]([Br:20])[CH:22]=4)=[O:15])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acidHCID 184588965-Bromo-6-methylpyridin-3-amine

Product 1

HCID 442061041-(benzo[d][1,3]dioxol-5-yl)-N-(5-bromo-6-methylpyridin-3-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-Benzo[1,3]dioxol-5-yl-cyclopropanecarboxylic acid (2.76 g, 13.4 mmol) was placed in an oven-dried flask under nitrogen. Thionyl chloride (3.0 mL) and N,N-dimethylformamide (0.3 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 10 mL of anhydrous dichloromethane. This solution was then slowly added to a solution of 5-bromo-6-methylpyridin-3-amine (2.50 g, 13.4 mmol) in 10 mL of anhydrous dichloromethane containing triethylamine (5.64 mL, 40.2 mmol). The resulting mixture was allowed to stir for 10 minutes at room temperature. The crude product was then washed three times with a saturated aqueous solution of sodium bicarbonate, followed by two washes with a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, evaporated to dryness, and the resulting yellow powder (3.62 g, 9.65 mmol, 72.0%) was used without further purification. ESI-MS m/z calc. 374.0, found; 375.1 (M+1)+ Retention time 2.30 minutes. 1H NMR (400 MHz, CD3CN) δ 8.38 (d, J=2.2 Hz, 1H), 8.14 (d, J=2.2 Hz, 1H), 7.80-7.60 (m, 1H), 7.08-6.95 (s, 2H), 6.89 (dd, J=1.2, 7.3 Hz, 1H), 6.01 (s, 2H), 2.54 (s, 3H), 1.59-1.50 (m, 2H), 1.19-1.09 (m, 2H).

Workup

  1. customThe excess thionyl chloride was removed under vacuum
  2. stirringto stir for 10 minutes at room temperature
  3. washThe crude product was then washed three times with a saturated aqueous solution of sodium bicarbonate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-a3d1b631d05046809ade69f1b85702ee
Source dataset
uspto-grants-2014_08
Patent number
US08796312B2

Reaction notes

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