Cesium carbonate → 6-chloro-2-methyl-4-(5-((1R,5S)-3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

HRID 1431197Notes

Reaction equation

HRID 1431197 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:11][N:12]1[CH2:18][CH:17]2[N:19]([C:20]3[CH:21]=[CH:22][C:23]([NH2:26])=[N:24][CH:25]=3)[CH:14]([CH2:15][CH2:16]2)[CH2:13]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:26][C:23]2[CH:22]=[CH:21][C:20]([N:19]3[C@H:14]4[CH2:15][CH2:16][C@@H:17]3[CH2:18][N:12]([CH3:11])[CH2:13]4)=[CH:25][N:24]=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 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 667431655-(3-Methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-amine

Product 1

HCID 667422686-chloro-2-methyl-4-(5-((1R,5S)-3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-ylamino)pyridazin-3(2H)-oneYield 47.8%

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 (492 mg, 2.20 mmol), 5-(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-amine (437 mg, 2.0 mmol), Xantphos (86.8 mg, 150 μmol) and cesium carbonate (1.95 g, 6.00 mmol) in dry dioxane (10 ml) was vacuum de-gassed and place under argon atmosphere. To this mixture was added tris(dibenzylideneacetone)dipalladium (0) (31.1 mg, 30 μmol) and the vacuum de-gas cycle was repeated. The reaction was heated at 90° C. (oil bath) with vigorous stirring overnight. The flask was cooled to ambient and the contents were filtered through a plug of celite, rinsing well with dioxane. The combined filtrate and washes were concentrated. The resultant crude residue was triturated with ether to provide the desired product as a light yellow solid (345 mg, 47.8%). (M+H)+=361.0, 363 m/e.

Workup

  1. customde-gassed
  2. customthe vacuum de-gas cycle
  3. temperatureThe flask was cooled to ambient and the contents
  4. filtrationwere filtered through a plug of celite
  5. washrinsing well with dioxane
  6. concentrationThe combined filtrate and washes were concentrated
  7. customThe resultant crude residue was triturated with ether

Sources & evidence

ORD record
ord-1c624ab7b6324ee585d16de5fb6bbce5
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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