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 1055664ノート

反応式

HRID 1055664 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-4719d4a40827453d9c7370b335da2a61
出典データセット
uspto-grants-2016_07
特許番号
US09394309B2

反応ノート

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