Cesium carbonate → HCID 67282367, compound

HRID 1910695Notes

Reaction equation

HRID 1910695 reaction equation
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH:8]1[C:14](=[O:15])[N:13]([CH3:16])[C:12]2[CH:17]=[CH:18][C:19]([Cl:21])=[CH:20][C:11]=2[C:10](Cl)=[N:9]1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:44](=[O:49])[C:45]([CH3:48])([CH3:47])[CH3:46])=[N:41][CH:42]=2)O1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C.O.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH:8]1[C:14](=[O:15])[N:13]([CH3:16])[C:12]2[CH:17]=[CH:18][C:19]([Cl:21])=[CH:20][C:11]=2[C:10]([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:44](=[O:49])[C:45]([CH3:46])([CH3:47])[CH3:48])=[N:41][CH:42]=2)=[N:9]1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 574164182,2-Dimethyl-N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]propanamideHCID 67283973HCID 67283973, compound

Product 1

HCID 67282367HCID 67282367, compoundYield 37.1%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(Biphenyl-2-ylmethyl)-5,7-dichloro-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (0.192 g, 0.469 mmol), N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)pivalamide (0.214 g, 0.703 mmol, 1.2 eq), Palladium (II) acetate (0.2 eq), triphenyl phosphine (0.2 eq) and cesium carbonate (2 eq) were heated at 100° C. in DMF (3 mL) under an atmosphere of nitrogen in a sealed tube for 1.5 h. The mixture was cooled then diluted with ethyl acetate and water (2:1) then filtered through a pad of celite. The layers were separated and the organic phase was washed with brine then dried over sodium sulfate. Chromatography eluting with 1:1 ethyl acetate in hexanes gave an oil which was dissolved in a 2:1 mixture of acetonitrile and water and freeze-dried to give product as an off-white solid (0.096 g, 37% yield). 1H-NMR (300 MHz, CDCl3) δ 8.29-8.22 (m, 2H), 8.09 (s, 1H), 7.71 (dd, 1H), 7.51-7.47 (m, 2H), 7.32-7.28 (m, 2H), 7.20-7.12 (m, 8H), 3.69-3.55 (m, 2H), 3.41-3.36 (m, 1H), 3.31 (s, 3H), 1.33 (s, 9H). MS (APCI) m/z 551 (M+1).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationthen filtered through a pad of celite
  3. customThe layers were separated
  4. washthe organic phase was washed with brine
  5. dry with materialthen dried over sodium sulfate
  6. washChromatography eluting with 1:1 ethyl acetate in hexanes
  7. customgave an oil which
  8. customfreeze-dried

Sources & evidence

ORD record
ord-aae44724aefe40bbb250d460784dca58
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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