Potassium Phosphate, Tribasic → HCID 68328034, compound

HRID 634117Notes

Reaction equation

HRID 634117 reaction equation
I[C:2]1[C:6]2=[N:7][C:8]([C:11]3[O:15][C:14]([NH2:16])=[N:13][N:12]=3)=[CH:9][CH:10]=[C:5]2[N:4](S(C2C=CC(C)=CC=2)(=O)=O)[CH:3]=1.[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:2]1[C:6]2=[N:7][C:8]([C:11]3[O:15][C:14]([NH2:16])=[N:13][N:12]=3)=[CH:9][CH:10]=[C:5]2[NH:4][CH:3]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343542-Fluorophenylboronic acidHCID 68328002HCID 68328002, compound

Product 1

HCID 68328034HCID 68328034, compoundYield 16.3%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
140 °C

Procedure

A glass microwave reaction vessel was charged with 5-(3-iodo-1-((4-methylphenyl)sulfonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-1,3,4-oxadiazol-2-amine (0.050 g, 0.104 mmol), 2-fluorophenylboronic acid (0.020 g, 0.145 mmol, Sigma-Aldrich), bis-(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.68 mg, 5.19 μmol) and K3PO4 (0.066 g, 0.312 mmol) in 70% i-PrOH in water (1.00 mL). The mixture was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 140° C. for 30 min. The layers were separated and the reaction vessel washed with MeOH. The organic washes were combined, filtered and purified by RP-HPLC (5-100% MeCN in H2O with 0.1% TFA over 20 min). Saturated NaHCO3 (aq.) was added to the tubes that contained the desired product. The mixture was extracted with 3/1 CHCl3/i-PrOH and the combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give 5-(3-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-1,3,4-oxadiazol-2-amine (0.005 g, 0.017 mmol, 16.30%). MS (ESI, pos. ion) m/z: 296.1 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.02-7.10 (m, 1H), 7.11-7.19 (m, 2H), 7.77-7.86 (m, 2H), 7.99 (d, J=2.93 Hz, 1H), 8.81-8.91 (m, 1H).

Workup

  1. customA glass microwave reaction vessel
  2. customThe layers were separated
  3. washthe reaction vessel washed with MeOH
  4. filtrationfiltered
  5. custompurified by RP-HPLC (5-100% MeCN in H2O with 0.1% TFA over 20 min)
  6. additionSaturated NaHCO3 (aq.) was added to the tubes that
  7. extractionThe mixture was extracted with 3/1 CHCl3/i-PrOH
  8. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f678b18c5b0c4648ac342c821e231507
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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