Cesium carbonate → tert-Butyl 4-[({2-[(2,3-difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}amino)sulfonyl]-1,4-diazepane-1-carboxylate

HRID 1025006노트

반응식

HRID 1025006 반응식
[NH2:1][S:2]([N:5]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:6]1)(=[O:4])=[O:3].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:60]1[CH:65]=[C:64]([O:66][CH3:67])[N:63]=[C:62]([S:68][CH2:69][C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[C:71]=2[F:77])[N:61]=1.[Cl-].[NH4+]>O1CCOCC1.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]>[F:77][C:71]1[C:72]([F:76])=[CH:73][CH:74]=[CH:75][C:70]=1[CH2:69][S:68][C:62]1[N:61]=[C:60]([NH:1][S:2]([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:6]2)(=[O:3])=[O:4])[CH:65]=[C:64]([O:66][CH3:67])[N:63]=1

참가 물질

8

반응물 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67051265Tert-butyl 4-sulfamoyl-1,4-diazepane-1-carboxylateHCID 866198774-Chloro-2-([(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine2회

생성물 1

HCID 53628411tert-Butyl 4-[({2-[(2,3-difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}amino)sulfonyl]-1,4-diazepane-1-carboxylate

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A mixture of tert-Butyl 4-(aminosulfonyl)-1,4-diazepane-1-carboxylate (the product of example 75, 0.277 g), tris(dibenzylideneacetone)-dipalladium (0) (45 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (24 mg), cesium carbonate (0.242 g) and 4-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine (the product of example 35 step i, 0.15 g) in anhydrous dioxane (6 ml) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 15 min. Saturated aqueous ammonium chloride was added and the resulting mixture extracted with EtOAc. The combined organic extracts were washed with saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica using a 1:19 to 3:7 mixture of EtOAc and iso-hexane as eluent to give the subtitle compound as a yellow oil. Yield: 0.223 g

후처리

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 15 min
  3. extractionthe resulting mixture extracted with EtOAc
  4. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography on silica using a 1:19
  9. additionto 3:7 mixture of EtOAc and iso-hexane as eluent

출처 및 근거

ORD 기록
ord-3f8831829212499d8b59f5115406d827
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722883B2

반응 노트

불러오는 중…