Cesium carbonate → 4-tert-Butyl-N-(3-(6-methoxy-5-(6-morpholinopyridazin-3-ylamino)pyridin-3-yl)-2-methylphenyl)benzamide

HRID 1174563Notes

Reaction equation

HRID 1174563 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:10]2[C:11]([CH3:29])=[C:12]([NH:16][C:17](=[O:28])[C:18]3[CH:23]=[CH:22][C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:20][CH:19]=3)[CH:13]=[CH:14][CH:15]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].Cl[C:31]1[N:36]=[N:35][C:34]([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)=[CH:33][CH:32]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.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]>[C:24]([C:21]1[CH:20]=[CH:19][C:18]([C:17]([NH:16][C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([C:4]3[CH:5]=[N:6][C:7]([O:8][CH3:9])=[C:2]([NH:1][C:31]4[N:36]=[N:35][C:34]([N:37]5[CH2:38][CH2:39][O:40][CH2:41][CH2:42]5)=[CH:33][CH:32]=4)[CH:3]=3)[C:11]=2[CH3:29])=[O:28])=[CH:23][CH:22]=1)([CH3:25])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 3210794-(6-Chloropyridazin-3-yl)morpholineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59557884N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4-tert-butylbenzamide

Product 1

HCID 595578954-tert-Butyl-N-(3-(6-methoxy-5-(6-morpholinopyridazin-3-ylamino)pyridin-3-yl)-2-methylphenyl)benzamideYield 22%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

A 48-mL seal tube equipped with a magnetic stirring bar was charged with N-(3-(5-amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4-tert-butylbenzamide (6) (0.39 g, 1.0 mmol), 4-(6-chloropyridazin-3-yl)morpholine (0.30 g, 1.5 mmol), Pd2(dba)3 (0.083 g, 0.10 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.075 g, 0.13 mmol), and Cs2CO3 (0.65 g, 2.0 mmol) in dioxane (15 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane (20 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-33%, MeOH in dichloromethane, to afford 0.12 g (22%) of 4-tert-butyl-N-(3-(6-methoxy-5-(6-morpholinopyridazin-3-ylamino)pyridin-3-yl)-2-methylphenyl)benzamide (7) as a solid.

Workup

  1. customA 48-mL seal tube
  2. customequipped with a magnetic stirring bar
  3. customAfter the mixture was degassed for 15 min.
  4. temperatureThen, the reaction mixture was cooled to room temperature
  5. additionpoured into H2O (10 mL)
  6. additionTo this was added dichloromethane (20 mL)
  7. customthe layers were separated
  8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  9. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe crude mixture was purified by column chromatography, gradient 0-33%, MeOH in dichloromethane

Sources & evidence

ORD record
ord-4411be4c111447d0b73c1ad20bddaf77
Source dataset
uspto-grants-2010_11
Patent number
US07838523B2

Reaction notes

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