Potassium Carbonate → 3-[6-Amino-5-(1,3-benzothiazol-2-yl)pyridin-3-yl]phenol

HRID 1926371Notes

Reaction equation

HRID 1926371 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:17])=[N:12][CH:13]=[C:14](Br)[CH:15]=1.[OH:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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]>[NH2:17][C:11]1[N:12]=[CH:13][C:14]([C:23]2[CH:24]=[C:19]([OH:18])[CH:20]=[CH:21][CH:22]=2)=[CH:15][C:10]=1[C:2]1[S:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 67389127HCID 67389127, compound

Product 1

HCID 675207593-[6-Amino-5-(1,3-benzothiazol-2-yl)pyridin-3-yl]phenol

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-benzothiazol-2-yl-5-bromopyridin-2-ylamine (BB7) (100 mg, 0.330 mmol), 3-hydroxyphenylboronic acid (68 mg, 0.49 mmol) and potassium carbonate (140 mg, 0.980 mmol) in 1,4-dioxane (4.5 mL) and H2O (1.5 mL) was degassed and refilled with argon (3×) prior to the addition of Pd(dppf)Cl2 (10 mg, 0.020 mmol). The reaction mixture was degassed and refilled with argon (2×) and left to stir at 100° C. for 30 min in the microwave reactor. Then, the mixture was passed through a pad of Celite and to the filtrate was partitioned between EtOAc and NaHCO3 aq. soln. (3×). The combined organic extracts were treated with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification via silica gel chromatography (5% MeOH in DCM) afforded the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=6.75-6.77 (m, 1H), 7.04-7.04 (m, 1H), 7.10-7.12 (m, 1H), 7.27 (t, J=8.0 Hz, 1H), 7.46-7.50 (m, 1H), 7.55-7.58 (m, 1H), 8.02 (br.s, 2H), 8.10-8.16 (m, 3H), 8.46 (d, J=4.0 Hz, 1H), 9.54 (s, 1H). MS (ES+): m/z=320.09 (100) [MH+]. HPLC: tR=3.44 min (ZQ3, polar—5 min).

Workup

  1. customwas degassed
  2. additionrefilled with argon (3×)
  3. customThe reaction mixture was degassed
  4. additionrefilled with argon (2×)
  5. waitleft
  6. customwas partitioned between EtOAc and NaHCO3 aq. soln
  7. additionThe combined organic extracts were treated with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification via silica gel chromatography (5% MeOH in DCM)

Sources & evidence

ORD record
ord-fc6c0a8950e0473fbdb42b6d397002f1
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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