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

HRID 1988880Notes

Reaction equation

HRID 1988880 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 4) (2.0 g), DIPEA (4 ml) and HATU (3.05 g) were dissolved in DMF (20 ml) and stirred at room temp for 15 min. 2-Aminothiadiazole (810 mg) was added and the mixture was stirred at room temp for 18 h. The solvent was evaporated under vacuum and the residue was partitioned between ethyl acetate (250 ml) and hydrochloric acid (2N, 150 ml). The aqueous phase was extracted with ethyl acetate (2×250 ml). The combined organic extracts were dried (magnesium sulphate) and the solvent was removed under vacuum. The residue was absorbed onto silica and purified by flash column chromatography eluting with cyclohexane/ethyl acetate (4:1 then 1:1) to give the title compound (0.95 g).

Workup

  1. stirringthe mixture was stirred at room temp for 18 h
  2. customThe solvent was evaporated under vacuum
  3. customthe residue was partitioned between ethyl acetate (250 ml) and hydrochloric acid (2N, 150 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×250 ml)
  5. dry with materialThe combined organic extracts were dried (magnesium sulphate)
  6. customthe solvent was removed under vacuum
  7. customThe residue was absorbed onto silica
  8. custompurified by flash column chromatography
  9. washeluting with cyclohexane/ethyl acetate (4:1

Sources & evidence

ORD record
ord-cf303f971b0a431f942b4788c2867749
Source dataset
uspto-grants-2010_01
Patent number
US07642276B2

Reaction notes

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