Potassium Carbonate → HCID 68291720, compound

HRID 1507936Notes

Reaction equation

HRID 1507936 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][CH2:11][CH2:12][CH3:13])=[C:8]([C:14]([NH2:16])=[O:15])[CH:7]=[N:6][N:5]2[CH:17]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:18]1([C:2]2[CH:3]=[C:4]3[C:9]([NH:10][CH2:11][CH2:12][CH3:13])=[C:8]([C:14]([NH2:16])=[O:15])[CH:7]=[N:6][N:5]3[CH:17]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 68291635HCID 68291635, compound2×

Product 1

HCID 68291720HCID 68291720, compoundYield 80.6%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
92.5 °C

Procedure

Nitrogen was bubbled through a mixture of 6-bromo-4-(propylamino) pyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 8, 20 mg, 0.067 mmol), phenylboronic acid (24.62 mg, 0.202 mmol), tetrakis(triphenylphosphine) palladium(0) (7.78 mg, 6.73 μmol) and potassium carbonate, 2M (0.135 mL, 0.269 mmol) in dimethoxyethane (0.6 mL) for ˜1 minute. The reaction mixture was then heated to 90-95° C. for 2 hr. The reaction mixture was partitioned between EtOAc (20 ml) and water (20 ml). The organic layer was washed with brine (20 ml), dried (MgSO4) and concentrated to a brown residue that was dissolved in MeOH and was subjected to preparative HPLC (Phenomenex 30×100 mm S-5 column; eluting with 45-90% aqueous MeOH+0.1% TFA over an 12 minute gradient, flow rate=1 mL/min, 220 wavelength detection). The product containing fraction was concentrated to afford the title compound (16 mg, 0.054 mmol, 80% yield) as a tan solid. HPLC (condition M): retention time=2.93 min.; LCMS (ES+) m/z: 295.14 (M+H); 1H NMR (400 MHz, MeOD) δ ppm 1.12 (t, J=7.3 Hz, 3 H), 1.77-1.87 (m, 2 H), 3.83 (t, J=6.5 Hz, 2 H), 7.20-7.31 (m, 2 H), 7.32-7.44 (m, 2 H), 7.66 (d, J=7.5 Hz, 2 H), 7.91 (s, 1 H), 8.09 (s, 1 H).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (20 ml) and water (20 ml)
  2. washThe organic layer was washed with brine (20 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated to a brown residue that
  5. dissolutionwas dissolved in MeOH
  6. washeluting with 45-90% aqueous MeOH+0.1% TFA over an 12 minute gradient, flow rate=1 mL/min, 220 wavelength detection)
  7. additionThe product containing fraction
  8. concentrationwas concentrated

Sources & evidence

ORD record
ord-b018285e126c4d4fb3a6c9e206c7f440
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

Loading…