Cesium carbonate → HCID 90411230, compound

HRID 626575Notes

Reaction equation

HRID 626575 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.Cl.[CH3:19][N:20]([CH3:29])[C@@H:21]1[CH2:25][CH2:24][N:23]([C:26]([NH2:28])=[O:27])[CH2:22]1.C([O-])([O-])=O.[Cs+].[Cs+].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>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]>[CH3:19][N:20]([CH3:29])[C@@H:21]1[CH2:25][CH2:24][N:23]([C:26]([NH:28][C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)=[O:27])[CH2:22]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridineHCID 90409521HCID 90409521, compound

Product 1

HCID 90411230HCID 90411230, compoundYield 97.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of Example A1 (0.500 g, 1.987 mmol), (R)-3-(dimethylamino)pyrrolidine-1-carboxamide hydrochloride (0.770 g, 3.97 mmol) and Cs2CO3 (1.295 g, 3.97 mmol) and Xantphos (0.230 g, 0.397 mmol) in dioxane (10 mL) was sparged with Ar, treated with Pd2(dba)3 (0.182 g, 0.199 mmol), sparged again with Ar and heated at 100° C. overnight. The mixture was cooled to RT, treated with THF, the solids removed via filtration, washed with THF and the filtrate concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc) to afford (R)-3-(dimethylamino)-N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)pyrrolidine-1-carboxamide (720 mg, 97%). MS (ESI) m/z: 373.1 (M+H+).

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with THF
  4. customthe solids removed via filtration
  5. washwashed with THF
  6. concentrationthe filtrate concentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/EtOAc)

Sources & evidence

ORD record
ord-21b0f79578c047809f78a1d92d4ef949
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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