Potassium Carbonate → HCID 68291180, compound

HRID 1507938Notes

Reaction equation

HRID 1507938 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([O:10][CH3:11])=[C:8]([C:12]([NH2:14])=[O:13])[CH:7]=[N:6][N:5]2[CH:15]=1.[C:16]1(B(O)O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.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>[CH3:11][O:10][C:9]1[C:4]2[N:5]([CH:15]=[C:2]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:3]=2)[N:6]=[CH:7][C:8]=1[C:12]([NH2:14])=[O:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 68291481HCID 68291481, compound

Product 1

HCID 68291180HCID 68291180, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
92.5 °C

Procedure

Nitrogen was bubbled through a mixture of 6-bromo-4-methoxypyrrolo[1,2-b]pyridazine-3-carboxamide (77 mg, 0.285 mmol), phenyl boronic acid (104 mg, 0.855 mmol), tetrakis(triphenylphosphine)palladium (32.9 mg, 0.029 mmol) and 2M aq. potassium carbonate, (0.570 mL, 1.140 mmol) in DME (0.75 mL) for ˜1 minute. The reaction mixture was then heated to 90-95° C. for 1 hr. The reaction mixture was partitioned between EtOAc (30 ml) and water (30 ml). The organic layer was washed with brine (30 ml), dried (MgSO4) and concentrated to afford a yellow solid that was chromatographed on a 12 g silica gel cartridge, eluting with a 0-100% EtOAc/hexanes gradient. The pure fractions were concentrated to a tan solid that was contaminated with a small amount of triphenylphosphine oxide. The material was triturated with ethyl ether to afford the title compound (62 mg, 0.229 mmol, 80% yield) as a tan solid. HPLC (condition M): retention time=2.36 min.; LCMS (ES+) m/z: 268.11 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 4.52 (s, 3 H), 5.73 (s, 1 H), 7.20 (d, J=1.8 Hz, 1 H), 7.27-7.35 (m, 2 H), 7.41-7.47 (m, 2 H), 7.63-7.68 (m, 2 H), 8.10 (d, J=1.8 Hz, 1 H), 8.69 (s, 1 H).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (30 ml) and water (30 ml)
  2. washThe organic layer was washed with brine (30 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto afford a yellow solid
  6. customthat was chromatographed on a 12 g silica gel cartridge
  7. washeluting with a 0-100% EtOAc/hexanes gradient
  8. concentrationThe pure fractions were concentrated to a tan solid
  9. customThe material was triturated with ethyl ether

Sources & evidence

ORD record
ord-e79f07374e2e4d978e9a77805e1643e4
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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