Potassium Carbonate → 3-(5-Chloro-8-fluoroisoquinolin-3-yl)-5-thiophen-3-ylpyridin-2-amine

HRID 1926323Notes

Reaction equation

HRID 1926323 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[CH:11][C:12]3[C:17]([CH:18]=2)=[C:16]([Cl:19])[CH:15]=[CH:14][C:13]=3[F:20])[C:5]([NH2:8])=[N:6][CH:7]=1.[S:21]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22]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]>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([F:20])=[C:12]2[C:17]=1[CH:18]=[C:9]([C:4]1[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:23]3[CH:24]=[CH:25][S:21][CH:22]=3)[CH:3]=1)[N:10]=[CH:11]2

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 581760Thiophene-3-boronic acidHCID 675207675-Bromo-3-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine

Product 1

HCID 675212113-(5-Chloro-8-fluoroisoquinolin-3-yl)-5-thiophen-3-ylpyridin-2-amine

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 5-bromo-3-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine (BB4) (25 mg, 0.070 mmol), 3-thienylboronic acid (20 mg, 0.10 mmol) and potassium carbonate (29 mg, 0.21 mmol) in 1,4-dioxane (1.0 mL) and H2O (0.4 mL) was degassed and refilled with argon (3×) prior to the addition of Pd(dppf)Cl2 (5 mg, 0.01 mmol). The reaction mixture was degassed and refilled with argon (2×) and left to stir at 100° C. in the microwave reactor for 30 min. Then, the mixture was passed through PL-Thiol MP SPE resin and concentrated in vacuo. The residual oil was partitioned between DCM and H2O. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification via MDP afforded the title compound as a yellow solid. MS (ES+): m/z=356.03/358.05 (100/50) [MH+]. HPLC: tR=3.22 min (ZQ2, 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. concentrationconcentrated in vacuo
  7. customThe residual oil was partitioned between DCM and H2O
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification via MDP

Sources & evidence

ORD record
ord-55a3989c98b049eeb61436478f1f8992
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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