Ammonia → tert-Butyl 4-[3-({4-methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-carbamoyl)-5-(pentafluoro-lambda6-sulphanyl)phenyl]piperazin-1-carboxylate

HRID 1055664노트

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HRID 1055664 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([CH:20]=[C:21]([S:23]([F:28])([F:27])([F:26])([F:25])[F:24])[CH:22]=2)[C:17]([OH:19])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:60][C:61]1[CH:67]=[CH:66][C:64]([NH2:65])=[CH:63][C:62]=1[N:68]1[C:75]2[N:71]([N:72]=[C:73]([C:76]3[CH:77]=[N:78][NH:79][CH:80]=3)[CH:74]=2)[CH:70]=[CH:69]1.N>CN(C=O)C>[CH3:60][C:61]1[CH:67]=[CH:66][C:64]([NH:65][C:17]([C:16]2[CH:15]=[C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]3)[CH:22]=[C:21]([S:23]([F:26])([F:28])([F:27])([F:24])[F:25])[CH:20]=2)=[O:19])=[CH:63][C:62]=1[N:68]1[C:75]2[N:71]([N:72]=[C:73]([C:76]3[CH:77]=[N:78][NH:79][CH:80]=3)[CH:74]=2)[CH:70]=[CH:69]1

참가 물질

7

반응물 5

HCID 222AmmoniaHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896995763-[4-(tert-Butoxycarbonyl)piperazin-1-yl]-5-(pentafluoro-lambda6-sulphanyl)benzoic acidHCID 1364091134-Methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]aniline

생성물 1

HCID 136409111tert-Butyl 4-[3-({4-methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-carbamoyl)-5-(pentafluoro-lambda6-sulphanyl)phenyl]piperazin-1-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

The compound from Example 16A (320 mg, 0.74 mmol) was dissolved in 2.3 ml of DMF, HATU (309 mg, 0.81 mmol) and then 4-methylmorpholine (0.32 ml) were added, and the mixture was stirred at RT for 30 min. At −5° C., the compound of Example 7A (103 mg, 0.37 mmol) was then added and the mixture was stirred at RT for 16 h. A few milliliters of concentrated aqueous ammonia solution were then added. The mixture was stirred at RT for 15 min and then extracted with ethyl acetate. The organic phase was washed with conc. sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The crude product was purified by preparative HPLC (Method 28). This gave 210 mg (purity 61%, 50% of theory) of the title compound which was used without further purification for the next synthesis step.

후처리

  1. stirringthe mixture was stirred at RT for 16 h
  2. stirringThe mixture was stirred at RT for 15 min
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with conc. sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by preparative HPLC (Method 28)
  9. customThis gave 210 mg (purity 61%, 50% of theory) of the title compound which was used without further purification for the next synthesis step

출처 및 근거

ORD 기록
ord-4719d4a40827453d9c7370b335da2a61
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394309B2

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