Cesium carbonate → HCID 67983726、化合物

HRID 1748220ノート

反応式

HRID 1748220 の反応式
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

参加物

7

反応物 4

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

生成物 1

HCID 67983726HCID 67983726、化合物

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 7237O-Xylene溶媒

反応条件

温度
120 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-d25f9025b52d4d3bb63aeba0a8d581f7
出典データセット
uspto-grants-2015_10
特許番号
US09150568B2

反応ノート

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