Cesium carbonate → HCID 67983726, compound

HRID 1748220Notes

Reaction equation

HRID 1748220 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]2[C:6]([C:9]([O:11][CH3:12])=[O:10])=[N:7][S:8][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH:55]12[NH:62][CH:59]([CH2:60][CH2:61]1)[CH2:58][CH:57]([O:63][CH2:64][C:65]1[C:66]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][C:74]=3[O:79][C:80]([F:83])([F:82])[F:81])=[N:67][O:68][C:69]=1[CH:70]1[CH2:72][CH2:71]1)[CH2:56]2>C1(C)C(C)=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:70]1([C:69]2[O:68][N:67]=[C:66]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][C:74]=3[O:79][C:80]([F:81])([F:82])[F:83])[C:65]=2[CH2:64][O:63][CH:57]2[CH2:56][CH:55]3[N:62]([C:2]4[CH:14]=[CH:13][C:5]5[C:6]([C:9]([O:11][CH3:12])=[O:10])=[N:7][S:8][C:4]=5[CH:3]=4)[CH:59]([CH2:60][CH2:61]3)[CH2:58]2)[CH2:71][CH2:72]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 66906285Methyl 6-bromobenzo[d]isothiazole-3-carboxylateHCID 67983256HCID 67983256, compound

Product 1

HCID 67983726HCID 67983726, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with methyl 6-bromobenzo[d]isothiazole-3-carboxylate (WO07056582, 85 mg, 0.31 mmol), cesium carbonate (220 mg, 0.68 mmol), tris(dibenzylideneacetone)dipalladium(0) (13 mg, 0.014 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos) (14 mg, 0.028 mmol), and degassed xylene (1.5 mL). The mixture was degassed for 10 minutes and then 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole (I-1H) (115 mg, 0.28 mmol) in xylene (1 mL) was added. The reaction flask was evacuated and backfilled with argon three times and then heated at 120° C. for 12 hours. The reaction mixture was cooled to rt, diluted with ethyl acetate and filtered through a CELITE® pad, the filtrate concentrated, and chromatographed on silica using linear gradient, 20-80%, EtOAc in Hexanes) to give the desired ester as a yellow solid. MS m/z 600.2 (M+1), 622.2. (M+23).

Workup

  1. customdegassed xylene (1.5 mL)
  2. customThe mixture was degassed for 10 minutes
  3. customThe reaction flask was evacuated
  4. temperatureThe reaction mixture was cooled to rt
  5. additiondiluted with ethyl acetate
  6. filtrationfiltered through a CELITE® pad
  7. concentrationthe filtrate concentrated
  8. customchromatographed on silica using linear gradient, 20-80%, EtOAc in Hexanes)

Sources & evidence

ORD record
ord-d25f9025b52d4d3bb63aeba0a8d581f7
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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