Potassium Carbonate → HCID 68349400, compound

HRID 1507943Notes

Reaction equation

HRID 1507943 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:36]1[CH:37]=[C:38]2[C:43]([NH:44][CH:45]([CH:47]3[CH2:49][CH2:48]3)[CH3:46])=[C:42]([C:50]([NH2:52])=[O:51])[CH:41]=[N:40][N:39]2[CH:53]=1.CN1CC(=O)OB([C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][N:65]=2)OC(=O)C1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:47]1([CH:45]([NH:44][C:43]2[C:38]3[N:39]([CH:53]=[C:36]([C:64]4[CH:69]=[CH:68][CH:67]=[CH:66][N:65]=4)[CH:37]=3)[N:40]=[CH:41][C:42]=2[C:50]([NH2:52])=[O:51])[CH3:46])[CH2:49][CH2:48]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 53378328HCID 53378328, compoundHCID 68291726HCID 68291726, compound2×

Product 1

HCID 68349400HCID 68349400, compoundYield 37.1%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

Pd2 dba3 (0.850 mg, 0.928 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (1.770 mg, 3.71 mmol) were added to a degassed (nitrogen bubbled through for ca. 10 min) solution of (+/−)-6-bromo-4-(1-cyclopropylethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 9, 20 mg, 0.062 mmol), 6-methyl-2-(pyridin-2-yl)-1,3,6,2-dioxazaborocane-4,8-dione (21.72 mg, 0.093 mmol), potassium carbonate (42.8 mg, 0.309 mmol) and copper (II) acetate (5.62 mg, 0.031 mmol). The vial was sealed (screw-cap) and immersed in an oil bath pre-heated to 100° C. The reaction was allowed to stir at this temperature for 2 hrs. After cooling to rt, the mixture was filtered and purified by direct injection onto a preparative HPLC (condition A) to give the title compound (7.63 mg, 0.023 mmol, 36.4% yield). HPLC (condition I): retention time=5.08 minutes. LC/MS (M+H)+=m/z 322.2. 1H NMR (500 MHz, MeOD) δ ppm 8.69 (1 H, d, J=4.99 Hz), 8.40-8.49 (1 H, m), 8.32-8.40 (1 H, m), 8.28 (1 H, s), 7.76 (1 H, td, J=6.59, 1.25 Hz), 7.68 (1 H, d, J=1.94 Hz), 7.52 (1 H, d, J=1.94 Hz), 4.12 (1 H, quin, J=6.45 Hz), 1.52 (2 H, d, J=6.38 Hz), 1.14-1.29 (1 H, m), 0.58-0.75 (1 H, m), 0.35-0.51 (1 H, m).

Workup

  1. customa degassed
  2. customThe vial was sealed
  3. custom(screw-cap)
  4. customimmersed in an oil bath
  5. temperatureAfter cooling to rt
  6. filtrationthe mixture was filtered
  7. custompurified by direct injection onto a preparative HPLC (condition A)

Sources & evidence

ORD record
ord-c596eab4964646dfa4f01a3804acd0da
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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