Isopropanol → HCID 44124820, compound

HRID 1692014Notes

Reaction equation

HRID 1692014 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19](B5OC(C)(C)C(C)(C)O5)[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:31]1[N:36]=[C:35]([C:37](OC)=[O:38])[CH:34]=[CH:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+].[CH:47]([OH:50])([CH3:49])[CH3:48]>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>[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([C:31]5[N:36]=[C:35]([C:37]([O:50][CH:47]([CH3:49])[CH3:48])=[O:38])[CH:34]=[CH:33][CH:32]=5)[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 16217886Methyl 6-bromopyridine-2-carboxylateHCID 66905591HCID 66905591, compound

Product 1

HCID 44124820HCID 44124820, compound

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A vial containing (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (Example 64A, 31 mg, 0.074 mmol), methyl 6-bromo-2-pyridinecarboxylate (16 mg, 0.074 mmol), K2CO3 (31 mg, 0.22 mmol) and bis(triphenylphosphine)palladium(II) chloride (5 mg, 7 μmol) suspended in isopropanol (1 mL) was heated to 80° C. for 2 hours. The mixture was allowed to stand at room temperature over night. The mixture was partitioned between 1 M NaOH (5 mL) and CH2Cl2 (25 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (25 mL). The combined CH2Cl2 layers were dried (MgSO4), filtered, concentrated and chromatographed on silica gel eluting with a gradient of 2% to 10% (9:1 methanol:ammonium hydroxide) in CH2Cl2 and then rechromatographed on silica gel eluting with a gradient of 10:1:1 to 7:1:1 ethyl acetate:HCO2H:H2O. The residue was partitioned between 1 M NaOH and CH2Cl2. This CH2Cl2 layer was dried (MgSO4), filtered and concentrated to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.42-1.52 (m, 2H), 1.44 (d, J=6.3 Hz, 6H), 1.59-1.68 (m, 4H), 1.96-2.11 (m, 1H), 2.26-2.36 (m, 1H), 2.41-2.59 (m, 4H), 2.95-3.08 (m, 1H), 3.46 (t, J=9.3 Hz, 1H), 3.53-3.63 (m, 1H), 3.75-3.84 (m, 1H), 3.85-3.94 (m, 1H), 5.29-5.39 (m, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.80-7.99 (m, 4H), 8.50 (d, J=1.2 Hz, 1H); MS (DCI/NH3) m/z 451 (M+H)+.

Workup

  1. waitto stand at room temperature over night
  2. customThe mixture was partitioned between 1 M NaOH (5 mL) and CH2Cl2 (25 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (25 mL)
  5. dry with materialThe combined CH2Cl2 layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed on silica gel eluting with a gradient of 2% to 10% (9:1 methanol:ammonium hydroxide) in CH2Cl2
  9. customrechromatographed on silica gel eluting with a gradient of 10:1:1 to 7:1:1 ethyl acetate
  10. customThe residue was partitioned between 1 M NaOH and CH2Cl2
  11. dry with materialThis CH2Cl2 layer was dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-4a6e4579be124521a2e9e43c6624436e
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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