Cyclopropanemethanamine → N-cyclopropylmethyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide

HRID 889326Notes

Reaction equation

HRID 889326 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[B:11]1[O:15][C:14]([CH3:17])([CH3:16])[C:13]([CH3:19])([CH3:18])[O:12]1.CCN(C(C)C)C(C)C.CN(C(ON1N=[N:44][C:39]2[CH:40]=[CH:41][CH:42]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1(CN)CC1>CN(C=O)C>[CH:40]1([CH2:39][NH:44][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([B:11]3[O:12][C:13]([CH3:19])([CH3:18])[C:14]([CH3:16])([CH3:17])[O:15]3)[CH:4]=2)[CH2:42][CH2:41]1

Participants

6

Reactant 4

HCID 75646CyclopropanemethanamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 160860864-Methyl-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid2×

Product 1

HCID 21914588N-cyclopropylmethyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamideYield 71.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid (Intermediate 17) (2.0 g, 7.63 mmol), DIPEA (4 ml, 22.89 mmol) and HATU (3.05 g, 8.02 mmol) were dissolved in DMF (20 ml) and stirred at room temperature for 15 mins. Cyclopropylmethylamine (568 mg, 8.01 mmol) was added and the reaction stirred at room temperature for 18 hours. The solvent was evaporated under vacuum and the reaction partitioned between ethyl acetate (250 ml) and water (50 ml). The organic phase was washed with hydrochloric acid (2N, 50 ml) and aqueous sodium bicarbonate (1M, 50 ml), then dried (magnesium sulphate) and the solvent evaporated under vacuum. The residue was absorbed onto silica and purified by flash column chromatography eluting with cyclohexane/ethyl acetate (4:1). The solvent was evaporated from the product fractions under vacuum to give N-cyclopropylmethyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (1.73 g). LCMS: retention time 3.47 min, MH− 316. NMR: δH [2H6]-DMSO 8.54,(1H, t), 8.11,(1H, d), 7.82,(1H, dd), 7.26,(1H, d), 3.12,(2H, t), 1.32,(12H, s), 1.03,(1H, m), 0.42,(2H, m), 0.22,(2H, m).

Workup

  1. stirringthe reaction stirred at room temperature for 18 hours
  2. customThe solvent was evaporated under vacuum
  3. customthe reaction partitioned between ethyl acetate (250 ml) and water (50 ml)
  4. washThe organic phase was washed with hydrochloric acid (2N, 50 ml) and aqueous sodium bicarbonate (1M, 50 ml)
  5. dry with materialdried (magnesium sulphate)
  6. customthe solvent evaporated under vacuum
  7. customThe residue was absorbed onto silica
  8. custompurified by flash column chromatography
  9. washeluting with cyclohexane/ethyl acetate (4:1)
  10. customThe solvent was evaporated from the product fractions under vacuum

Sources & evidence

ORD record
ord-9b2027f0af3e4ea29fe1fa812c5229fa
Source dataset
uspto-grants-2012_08
Patent number
US08252818B2

Reaction notes

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