Cesium carbonate → 4-(4-Chlorobenzyl)-2-(pyridin-4-yl)-5-(1H-pyrrol-2-yl)thiazole

HRID 2401785Notes

Reaction equation

HRID 2401785 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1.O1CCOCC1.C(OC([N:34]1[CH:38]=[CH:37][CH:36]=[C:35]1B(O)O)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=3)[S:6][C:2]=2[C:35]2[NH:34][CH:38]=[CH:37][CH:36]=2)=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 667479255-Bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole

Product 1

HCID 667488684-(4-Chlorobenzyl)-2-(pyridin-4-yl)-5-(1H-pyrrol-2-yl)thiazoleYield 29%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 5-bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole (94.0 mg, 0.257 mmol) in 4:1 dioxane:water (3.0 mL) was added 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (57 mg, 0.27 mmol), cesium carbonate (251 mg, 0.771 mmol), and tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.026 mmol). The solution was degassed with argon and heated in a microwave reactor at 130° C. for 105 minutes. The reaction was concentrated in vacuo and the residue taken up in DCM (25 mL) and water (10 mL). The layers were separated and the aqueous layer was extracted with DCM (2×10 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→80/20) followed by HPLC purification (formic acid method) to give 26 mg of the title compound as a yellow solid (29% yield). LC/MS (FA) ES+ 352. 1H NMR (300 MHz, d4-MeOH) δ: 8.62-8.60 (m, 2H), 7.90-7.88 (m, 2H), 7.66-7.55 (m, 1H), 7.26-7.24 (m, 2H), 7.20-7.17 (m, 2H), 6.92 (dd, 1H, J=2.7, 1.5 Hz), 6.32 (dd, 1H, J=3.5, 1.5 Hz), 6.21 (dd, 1H, J=3.5, 2.7 Hz), 4.28 (s, 2H).

Workup

  1. customThe solution was degassed with argon
  2. concentrationThe reaction was concentrated in vacuo
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (2×10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→80/20)
  9. customfollowed by HPLC purification (formic acid method)

Sources & evidence

ORD record
ord-eb121c21f3ed4ca598cef4124701fd87
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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