Potassium Phosphate, Tribasic → Pyridine, 5-(3-bromo-1,2,4-thiadiazol-5-yl)-3-chloro-2-(1-methylethoxy)-

HRID 1942676Notes

Reaction equation

HRID 1942676 reaction equation
[Cl:1][C:2]1[C:3]([O:17][CH:18]([CH3:20])[CH3:19])=[N:4][CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.[Br:21][C:22]1[N:26]=[C:25](Cl)[S:24][N:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:21][C:22]1[N:26]=[C:25]([C:6]2[CH:7]=[C:2]([Cl:1])[C:3]([O:17][CH:18]([CH3:19])[CH3:20])=[N:4][CH:5]=2)[S:24][N:23]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27250533-Bromo-5-chloro-1,2,4-thiadiazoleHCID 580424553-Chloro-2-isopropoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridine

Product 1

HCID 58494110Pyridine, 5-(3-bromo-1,2,4-thiadiazol-5-yl)-3-chloro-2-(1-methylethoxy)-Yield 96.4%

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Procedure

3-chloro-2-[(1-methylethyl)oxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (D108) (1.2 g, 4.03 mmol), 3-bromo-5-chloro-1,2,4-thiadiazole (1.609 g, 8.06 mmol), tripotassium phosphate (2.57 g, 12.10 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.329 g, 0.403 mmol) were heated by Biotage Initiator to 80° C. for 1 hr. The reaction mixture was concentrated and the slurry was diluted with ethyl acetate. The resulted solution was washed with water, dried and purified by ISCO column chromatography to afford 5-(3-bromo-1,2,4-thiadiazol-5-yl)-3-chloro-2-[(1-methylethyl)oxy]pyridine (D109) (1.3 g). δH (CDCl3, 400 MHz): 1.43 (6H, d), 5.45 (1H, m), 8.21 (1H, d), 8.59 (1H, d). MS (ES): C10H9BrClN3OS requires 332.9. found 334.0 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe slurry was diluted with ethyl acetate
  3. washThe resulted solution was washed with water
  4. customdried
  5. custompurified by ISCO column chromatography

Sources & evidence

ORD record
ord-4f6fd25b7bdc45ea8f0951d865c11940
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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