Potassium Carbonate → Hydrochloric Acid

HRID 912014Notes

Reaction equation

HRID 912014 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17](B3OC(C)(C)C(C)(C)O3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Br[C:29]1[C:33]2[CH:34]=[N:35][C:36]([NH2:50])=[C:37]([O:38][CH:39]([C:41]3[C:46]([Cl:47])=[CH:45][CH:44]=[C:43]([F:48])[C:42]=3[Cl:49])[CH3:40])[C:32]=2[O:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.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>[Cl:49][C:42]1[C:43]([F:48])=[CH:44][CH:45]=[C:46]([Cl:47])[C:41]=1[CH:39]([O:38][C:37]1[C:32]2[O:31][CH:30]=[C:29]([C:17]3[CH:16]=[N:15][N:14]([CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[CH:18]=3)[C:33]=2[CH:34]=[N:35][C:36]=1[NH2:50])[CH3:40].[ClH:47]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 674022843-Bromo-7-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Product 2

HCID 313Hydrochloric AcidHCID 578124837-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(1-piperidin-4-yl-1H-pyrazol-4-yl)-furo[3,2-c]pyridin-6-ylamine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (26.94 mg, 0.071 mmol), 3-bromo-7-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine (20.0 mg, 0.047 mmol), potassium carbonate (19.7 mg, 0.14 mmol) in DME (2.0 mL) and H2O (0.40 mL) was added Pd(PPh3)4 (2.8 mg, 0.0024 mmol) under Nitrogen. The resulting mixture was refluxed at 100° C. for 30 min. LC-MS indicated completion of reaction. The solvent was then removed under reduced pressure and the resulting residue was purified by a flash chromatography (2% MeOH in DCM). MS (ES+): m/z 590.07, 592.08 (MH+). HPLC: tR=3.48 min (ZQ3, polar—5 min). The product purified above was then dissolved in 2 mL dioxane, to this solution was added solution of 4 N HCl in dioxane (1 mL) at r.t., the resulting mixture was stirred at r.t. for 1.5 h. LC-MS indicated completion of reaction. The solvent was removed under reduced pressure to give the title compound as HCl salt. The 1H NMR spectrum matches that of Example 5.

Workup

  1. customcompletion of reaction
  2. customThe solvent was then removed under reduced pressure
  3. customthe resulting residue was purified by a flash chromatography (2% MeOH in DCM)
  4. custom5 min
  5. customThe product purified above
  6. dissolutionwas then dissolved in 2 mL dioxane, to this solution
  7. additionwas added solution of 4 N HCl in dioxane (1 mL) at r.t.
  8. customcompletion of reaction
  9. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-e37e9154ed2f4b948cfd02b8cc6ea934
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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