Cesium carbonate → HCID 71271269, compound

HRID 1752458Notes

Reaction equation

HRID 1752458 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[O:9][CH2:10][C:11]([F:24])([F:23])[C@:12]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[C:17](Br)[N:16]=2)([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[C:26]([C:28]1[CH:29]=[C:30]([CH3:37])[C:31]([C:34]([NH2:36])=[O:35])=[N:32][CH:33]=1)#[N:27].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.C(OCC)(=O)C.C(=O)(O)[O-].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:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[O:9][CH2:10][C:11]([F:24])([F:23])[C@:12]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[C:17]([NH:36][C:34]([C:31]3[C:30]([CH3:37])=[CH:29][C:28]([C:26]#[N:27])=[CH:33][N:32]=3)=[O:35])[N:16]=2)([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 666659355-Cyano-3-methyl-2-pyridinecarboxamideHCID 86689144HCID 86689144, compound

Product 1

HCID 71271269HCID 71271269, compoundYield 38%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 769Bicarbonate IonSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A degassed mixture of [(R)-4-(6-bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazine-2-yl]-carbamic acid tert-butyl ester (70 mg, 0.145 mmol), 5-cyano-3-methyl-pyridine-2-carboxylic acid amide (25.7 mg, 0.160 mmol), Xantphos (30.2 mg, 0.052 mmol), caesium carbonate (67.6 mg, 0.203 mmol) and Pd2(dba)3 (16.45 mg, 0.017 mmol) was heated under argon in dioxane (2.9 ml) at 60° C. for 5 hours. The reaction mixture (grey-brown suspension) was diluted with ethyl acetate and aq. bicarbonate solution and was then filtered. The filtrate was washed with water and brine, dried over sodium sulfate, filtered and evaporated. 166 mg brown solid. The crude product was chromatographed over silica gel (toluene/ethyl acetate 7:3) to give the title compound as a white solid. 28 mg (38% yield).

Workup

  1. filtrationwas then filtered
  2. washThe filtrate was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was chromatographed over silica gel (toluene/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-cdd32f1d1fcf4d4499424cd95f6940b6
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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