Cesium carbonate → HCID 66742595, compound

HRID 337295Notes

Reaction equation

HRID 337295 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[N:5]=[C:6]([Cl:8])[CH:7]=1.[N:11]1([CH2:15][C:16]([CH3:26])([O:18][C:19]2[CH:20]=[CH:21][C:22]([NH2:25])=[N:23][CH:24]=2)[CH3:17])[CH2:14][CH2:13][CH2:12]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[N:11]1([CH2:15][C:16]([CH3:26])([CH3:17])[O:18][C:19]2[CH:20]=[CH:21][C:22]([NH:25][C:2]3[C:3](=[O:10])[N:4]([CH3:9])[N:5]=[C:6]([Cl:8])[CH:7]=3)=[N:23][CH:24]=2)[CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 71008574HCID 71008574, compound

Product 1

HCID 66742595HCID 66742595, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-Bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.18 g, 9.75 mmol, Eq: 1.30), 5-(1-(azetidin-1-yl)-2-methylpropan-2-yloxy)pyridin-2-amine (1.66 g, 7.5 mmol, Eq: 1.00), Xantphos (651 mg, 1.13 mmol, 0.15 equiv) and Cs2CO3 (8.55 g, 26.3 mmol, 3.5 equiv) were combined in dioxane and the reaction mixture was degassed under vacuum with argon displacement. To the solution was added the Pd2(dba)3 (515 mg, 563 μM, 0.075 equiv) and the mixture was degassed again with argon. The reaction mixture was stirred under argon at 90° C. for 18 hrs before cooling to ambient temperature. The reaction mixture was filtered through a plug of celite. The celite cake was washed with THF and dichloromethane. The combined filtrate and washes were concentrated in vacuo. The crude product was purified by Analogix MPLC (60 g column; elute with 0.5% to 15% MeOH/DCM) to afford the desired product (1.43 g) as a tan solid. (M+H)+=364 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.24 (s, 6 H) 2.12 (quin, J=7.08 Hz, 2 H) 2.59 (s, 2 H) 3.35 (t, J=6.99 Hz, 4 H) 3.81 (s, 3 H) 6.83 (d, J=8.69 Hz, 1 H) 7.32 (dd, J=8.88, 2.83 Hz, 1 H) 8.09 (d, J=3.02 Hz, 1 H) 8.18 (s, 1 H) 8.25 (s, 1 H).

Workup

  1. customthe reaction mixture was degassed under vacuum with argon displacement
  2. customthe mixture was degassed again with argon
  3. temperaturebefore cooling to ambient temperature
  4. filtrationThe reaction mixture was filtered through a plug of celite
  5. washThe celite cake was washed with THF and dichloromethane
  6. concentrationThe combined filtrate and washes were concentrated in vacuo
  7. customThe crude product was purified by Analogix MPLC (60 g column; elute with 0.5% to 15% MeOH/DCM)

Sources & evidence

ORD record
ord-7b44300c63594cedb2943057cce59870
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

Loading…