Hydrochloric Acid → HCID 67960020, compound

HRID 1529328Notes

Reaction equation

HRID 1529328 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7](C1CCCCO1)[N:6]=[C:5]2[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([N:23]2[CH2:28][CH2:27][CH:26]([NH:29]C(=O)OC(C)(C)C)[CH2:25][CH2:24]2)[N:18]=1.[CH3:37][O:38][C:39]1[CH:40]=[N:41][CH:42]=[C:43](B2OC(C)(C)C(C)(C)O2)[CH:44]=1.C([O-])([O-])=O.[Na+].[Na+].Cl.CC(O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1.O>[CH3:37][O:38][C:39]1[CH:44]=[C:43]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][N:6]=[C:5]3[C:17]2[CH:22]=[CH:21][N:20]=[C:19]([N:23]3[CH2:24][CH2:25][CH:26]([NH2:29])[CH2:27][CH2:28]3)[N:18]=2)[CH:42]=[N:41][CH:40]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 38661613-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 67960194HCID 67960194, compound

Product 1

HCID 67960020HCID 67960020, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
145 °C

Procedure

A glass microwave reaction vessel was charged with tert-butyl 1-(4-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-ylcarbamate (0.305 g, 0.547 mmol), 3-methoxypyridine-5-boronic acid pinacol ester (0.232 g, 0.987 mmol, Frontier Scientific), Na2CO3 (0.356 g, 3.36 mmol) and trans-dichlorobis(triphenyl-phosphine)palladium (II) (0.056 g, 0.080 mmol). Water (2 mL) and dioxane (5 mL) were added and the reaction mixture was sealed under argon and heated in an Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 145° C. for 20 min. The reaction mixture was partitioned between DCM/brine and the aqueous layer was extracted with DCM (3×). The combined organic layers were evaporated onto silica gel and purified by flash chromatography (Isco, (40 gram)) eluting with 2M NH3 in MeOH:DCM (0:1→1:39) to give a white amorphous solid. The material was heated at 50° C. for 5 h in the presence of HCl, 5-6N in IPA (10 mL, 50.0 mmol). The mixture was cooled to RT and the solvent was removed in vacuo. The residue was dissolved in DMSO and purified by reverse-phase HPLC (Gilson; Gemini-NX 10μ C18 110 A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O:0.1% TFA ACN (9:1→1:9). The fractions containing the desired product were combined and concentrated in vacuo to give an off-white amorphous solid. m/z: 402.2 [M+1].

Workup

  1. customA glass microwave reaction vessel
  2. customthe reaction mixture was sealed under argon
  3. customThe reaction mixture was partitioned between DCM/brine
  4. extractionthe aqueous layer was extracted with DCM (3×)
  5. customThe combined organic layers were evaporated onto silica gel
  6. custompurified by flash chromatography (Isco, (40 gram))
  7. washeluting with 2M NH3 in MeOH:DCM (0:1→1:39)
  8. customto give a white amorphous solid
  9. temperatureThe mixture was cooled to RT
  10. customthe solvent was removed in vacuo
  11. dissolutionThe residue was dissolved in DMSO
  12. custompurified by reverse-phase HPLC (Gilson
  13. washGemini-NX 10μ C18 110 A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O
  14. additionThe fractions containing the desired product
  15. concentrationconcentrated in vacuo
  16. customto give an off-white amorphous solid

Sources & evidence

ORD record
ord-4803b135062c4308bc5403a470437931
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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