Hydrochloric Acid → 6-(3-Ethylureido)-4-(4-phenylthiazol-2-yl)pyridin-3-ylboronic acid

HRID 2061852Notes

Reaction equation

HRID 2061852 reaction equation
Br[C:2]1[C:3]([C:14]2[S:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:18]=2)=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[Li+].CCC[CH2-].[B:35](OC)([O:38]C)[O:36]C.Cl>C1COCC1.O>[CH2:12]([NH:11][C:9](=[O:10])[NH:8][C:5]1[N:6]=[CH:7][C:2]([B:35]([OH:38])[OH:36])=[C:3]([C:14]2[S:15][CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:18]=2)[CH:4]=1)[CH3:13]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 61028n-Butyl lithiumHCID 592085041-(5-Bromo-4-(4-phenylthiazol-2-yl)pyridin-2-yl)-3-ethylurea2×HCID 178418918HCID 178418918, compound

Product 1

HCID 594161886-(3-Ethylureido)-4-(4-phenylthiazol-2-yl)pyridin-3-ylboronic acidYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of 1-(5-bromo-4-(4-phenylthiazol-2-yl)pyridin-2-yl)-3-ethylurea (2.97 g, 7.36 mmol, Intermediate 15) in THF (25 mL) was cooled to −78° C. Isopropylmagnesium chloride (2.0M in THF; 8.84 mL, 17.67 mmol, Aldrich) was added slowly and the reaction was slowly warmed to −15° C. before being cooled back down to −78° C. N-Butyllithium (2.5M in hexanes; 14.73 mL, 36.82 mmol, Aldrich) was then added and the reaction was stirred at −78° C. for 1 hour. Trimethyl borate (8.21 mL, 73.64 mmol, Aldrich) was added all at once and an exotherm was observed. Following the exotherm, the reaction mixture was allowed to warm to room temperature and stir for 3 h. The reaction mixture was then cooled to 0° C. and 20 mL of water was added slowly followed by 10 mL of 6N HCl. The reaction mixture was allowed to warm to room temperature and stir for 30 min The reaction mixture was concentrated under reduced pressure to remove THF. The aqueous portion was diluted with 1N NaOH and diethylether. The impurities went into the ether layer (yellow) and the remaining white solid was filtered, washed with water and dried. The solid was then triturate with dilute acid (pH 4.5) to remove salts. The solid was dried overnight to yield product as a white solid (1.60 g).

Workup

  1. temperaturebefore being cooled back down to −78° C
  2. temperatureto warm to room temperature
  3. stirringstir for 3 h
  4. temperatureThe reaction mixture was then cooled to 0° C.
  5. temperatureto warm to room temperature
  6. stirringstir for 30 min The reaction mixture
  7. concentrationwas concentrated under reduced pressure
  8. customto remove THF
  9. additionThe aqueous portion was diluted with 1N NaOH and diethylether
  10. filtrationthe remaining white solid was filtered
  11. washwashed with water
  12. customdried
  13. customThe solid was then triturate
  14. additionwith dilute acid (pH 4.5)
  15. customto remove salts
  16. customThe solid was dried overnight

Sources & evidence

ORD record
ord-6d592d732b0d4b1588ab841ca70f09b4
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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