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

HRID 31415

Reaction equation

HRID 31415 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[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(O[N:37]1[N:45]=NC2C=CC=[N:43][C:38]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.NN1NC=[CH:56][S:55]1>CN(C=O)C>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:43][C:38]2[S:55][CH:56]=[N:45][N:37]=2)=[O:7])=[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

Participants

6

Reactant 4

HCID 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×HCID 219145783H-thiadiazol-2-amine

Product 1

HCID 586565324-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-([1,3,4]thiadiazol-2-yl)-benzamideYield 36.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid (Intermediate 21) (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. 2-Aminothiadiazole (810 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 hydrochloric acid (2N, 150 ml). The aqueous phase was extracted with ethylacetate (2×250 ml). The combined organic extracts were 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 then 1:1). The solvent was evaporated from the product fractions under vacuum to give 4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-([1,3,4]thiadiazol-2-yl)-benzamide (0.95 g).

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 hydrochloric acid (2N, 150 ml)
  4. extractionThe aqueous phase was extracted with ethylacetate (2×250 ml)
  5. dry with materialThe combined organic extracts were dried (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-d71d058c0ad34cd4b0dd5b87d3d4c68a
Source dataset
uspto-grants-2008_09
Patent number
US07425555B2

Linked notes

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