Potassium Phosphate, Tribasic → HCID 89962112, compound

HRID 877427Notes

Reaction equation

HRID 877427 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[S:8][C:4]=2[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:25][C:26]1[CH:31]=[C:30](B(O)O)[CH:29]=[CH:28][N:27]=1>O1CCOCC1.O.[Pd]>[F:25][C:26]1[CH:31]=[C:30]([C:2]2[CH:16]=[CH:15][C:5]3[N:6]=[C:7]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[S:8][C:4]=3[CH:3]=2)[CH:29]=[CH:28][N:27]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27833962-Fluoropyridine-4-boronic acidHCID 21041509Ethyl 6-bromo-2-benzothiazoleacetate

Product 1

HCID 89962112HCID 89962112, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

SiliaCat DPP-Pd (0.26 mmol/g loading, from Silicycle, 100 mg, 0.67 mmol), ethyl 2-(6-bromobenzo[d]thiazol-2-yl)acetate (described in WO2011/074560, 200 mg, 0.67 mmol), potassium phosphate (348 mg, 2.00 mmol) and (2-fluoropyridin-4-yl)boronic acid (141 mg, 1.00 mmol) in dioxane (5 mL)/water (0.2 mL) were purged with argon for 5 minutes and then heated at 90° C. After 4 hours, the reaction mixture was diluted with water (50 mL), extracted with DCM (3×50 mL), dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes over 15 minutes) to give Compound B23a (120 mg, 57% yield) as a brown solid. HPLC: RT=0.95 min (LCMS Method M). MS (ES): m/z=316.9 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.68 (d, J=1.7 Hz, 1H), 8.35 (d, J=5.2 Hz, 1H), 8.12 (d, J=8.5 Hz, 1H), 8.02 (dd, J=8.5, 1.9 Hz, 1H), 7.81 (d, J=5.2 Hz, 1H), 7.64 (s, 1H), 4.38 (s, 2H), 4.19 (q, J=7.1 Hz, 2H), 1.24 (t, J=7.0 Hz, 3H).

Workup

  1. extractionextracted with DCM (3×50 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes over 15 minutes)
  5. customto give Compound B23a (120 mg, 57% yield) as a brown solid

Sources & evidence

ORD record
ord-8645afc3d86c44a2ad6fea796c824bd3
Source dataset
uspto-grants-2015_03
Patent number
US08987314B2

Reaction notes

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