Cesium fluoride → HCID 68183056, compound

HRID 1615535Notes

Reaction equation

HRID 1615535 reaction equation
[N:1]1([C:7]2[S:8][C:9]3[C:10](=[O:21])[NH:11][CH2:12][CH:13]=[C:14]([Sn](C)(C)C)[C:15]=3[N:16]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:22][O:23][C:24](=[O:33])[C:25]1[CH:30]=[C:29](Br)[CH:28]=[CH:27][C:26]=1[Cl:32].[F-].[Cs+]>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:32][C:26]1[CH:27]=[CH:28][C:29]([C:14]2[C:15]3[N:16]=[C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[S:8][C:9]=3[C:10](=[O:21])[NH:11][CH2:12][CH:13]=2)=[CH:30][C:25]=1[C:24]([O:23][CH3:22])=[O:33]

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 842098Methyl 5-bromo-2-chlorobenzoateHCID 68182908HCID 68182908, compound

Product 1

HCID 68183056HCID 68183056, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-(morpholin-4-yl)-8-(trimethylstannyl)-5,6-dihydro-4H-[1,3]thiazolo[5,4-c]azepin-4-one (0.160 g, 0.386 mmol) and methyl-5-bromo-2-chlorobenzoate (0.116 g, 0.464 mmol) in DMF (3.74 mL) was purged with argon, and then cesium fluoride (0.205 g, 1.35 mmol), copper(I) iodide (0.0184 g, 0.0966 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0446 g, 0.0386 mmol) were added. The mixture was stirred at 80° C. for 2 hours. The solution was cooled to room temperature and some of the solvent was removed in vacuo. The residue was diluted with EA and water. The layers were separated and the aqueous layer was extracted twice more with EA. The combined organic layer was then washed with water and brine then dried over anhydrous sodium sulfate and concentrated. The residue was purified using column chromatography on silica gel (12 gr Analogix column, gradient DCM to 60% EA in DCM over 15 minutes) to give the product (0.129 g, 80%). LCMS: (AA) ES+ 420, 422. 1H NMR (400 MHz, d6-DMSO) δ: 8.05 (t, J=5.0 Hz, 1H), 7.80 (d, J=2.1 Hz, 1H), 7.61-7.44 (m, 2H), 6.48 (t, J=7.1 Hz, 1H), 3.84 (s, 3H), 3.70-3.62 (m, 4H), 3.61-3.53 (m, 2H), 3.42-3.34 (m, 4H).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customsome of the solvent was removed in vacuo
  3. additionThe residue was diluted with EA and water
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice more with EA
  6. washThe combined organic layer was then washed with water and brine
  7. dry with materialthen dried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified
  10. customon silica gel (12 gr Analogix column, gradient DCM to 60% EA in DCM over 15 minutes)

Sources & evidence

ORD record
ord-536a78a724b44172b0b29dbfa76c4dcf
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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