Cesium carbonate → Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

HRID 449693Notes

Reaction equation

HRID 449693 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[N:5]=[C:6]([Cl:8])[CH:7]=1.[NH2:11][C:12]1[N:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:14][CH:13]=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]>[Cl:8][C:6]1[CH:7]=[C:2]([NH:11][C:12]2[N:17]=[CH:16][C:15]([CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)[C:3](=[O:10])[N:4]([CH3:9])[N:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 49839963tert-Butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylateHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 66742247Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylateYield 71.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A solution of 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.42 g, 10.8 mmol), tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate (2.73 mg, 9.83 mmol), Xantphos (853 mg, 1.47 mmol) and cesium carbonate (9.61 g, 29.5 mmol) in dry dioxane (80 ml) was vacuum de-gassed and place under an argon atmosphere. To this mixture was added tris(dibenzylideneacetone)dipalladium (0) (203 mg, 197 mmol) and the vacuum de-gas cycle was repeated. The material was heated at 90° C. (oil bath) with vigorous stirring overnight. The flask was cooled to ambient temperature and the contents were filtered through a plug of celite, rinsing well with dioxane, the filtrate concentrated and the resulting residue triturated with 1; 1 ratio of ether/ethyl acetate. This provided the desired product as an off-white powder (2.73 g, 71.2%). (M+H)+=420.2 m/e.

Workup

  1. customde-gassed
  2. customthe vacuum de-gas cycle
  3. temperatureThe flask was cooled to ambient temperature
  4. filtrationthe contents were filtered through a plug of celite
  5. washrinsing well with dioxane
  6. concentrationthe filtrate concentrated
  7. customthe resulting residue triturated with 1

Sources & evidence

ORD record
ord-97b4d57bb8ce4a3aa4975ff315c9f7d9
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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