Ammonia → 3-(2-Hydroxypropan-2-yl)-N-{4-methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]-phenyl}-5-(pentafluoro-lambda6-sulphanyl)benzamide

HRID 1055705Notes

Reaction equation

HRID 1055705 reaction equation
[CH3:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[N:9]1[C:16]2[N:12]([N:13]=[C:14]([C:17]3[CH:18]=[N:19][NH:20][CH:21]=3)[CH:15]=2)[CH:11]=[CH:10]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[OH:53][C:54]([C:57]1[CH:58]=[C:59]([CH:63]=[C:64]([S:66]([F:71])([F:70])([F:69])([F:68])[F:67])[CH:65]=1)[C:60](O)=[O:61])([CH3:56])[CH3:55].N>CN(C=O)C>[OH:53][C:54]([C:57]1[CH:58]=[C:59]([CH:63]=[C:64]([S:66]([F:71])([F:67])([F:68])([F:69])[F:70])[CH:65]=1)[C:60]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([CH3:1])=[C:3]([N:9]2[C:16]3[N:12]([N:13]=[C:14]([C:17]4[CH:18]=[N:19][NH:20][CH:21]=4)[CH:15]=3)[CH:11]=[CH:10]2)[CH:4]=1)=[O:61])([CH3:55])[CH3:56]

Participants

7

Reactant 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 86690975HCID 86690975, compoundHCID 1364091134-Methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]aniline

Product 1

HCID 1364091123-(2-Hydroxypropan-2-yl)-N-{4-methyl-3-[6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]-phenyl}-5-(pentafluoro-lambda6-sulphanyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound from Example 7A (2.63 g, 9.45 mmol) was dissolved in 55 ml of DMF. HATU (7.91 g, 20.8 mmol) and N-methylmorpholine (8.31 ml, 75.6 mmol) were added, and the mixture was stirred at RT for 30 min. The mixture was then cooled to −5° C. and the compound from Example 19A (5.79 g, 18.9 mmol) was added. The mixture was stirred for a further 45 min, concentrated aqueous ammonia solution was then added and the mixture was stirred for another 15 min. The mixture was then extracted with ethyl acetate, and the organic extract was washed with conc. sodium chloride solution, dried over sodium sulphate and concentrated. The crude product was purified by preparative HPLC [column: Waters Sunfire C-18.5 μm, 250 mm×20 mm; ternary gradient water/acetonitrile/1% TFA in water: 0-6.7 min 45:50:5, ramp, 6.9-9.0 min 0:95:5]. This gave 3.86 g (72% of theory) of the title compound.

Workup

  1. temperatureThe mixture was then cooled to −5° C.
  2. stirringThe mixture was stirred for a further 45 min
  3. stirringthe mixture was stirred for another 15 min
  4. extractionThe mixture was then extracted with ethyl acetate
  5. extractionthe organic extract
  6. washwas washed with conc. sodium chloride solution
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated
  9. customThe crude product was purified by preparative HPLC [column: Waters Sunfire C-18.5 μm, 250 mm×20 mm; ternary gradient water/acetonitrile/1% TFA in water: 0-6.7 min 45:50:5, ramp, 6.9-9.0 min 0:95:5]

Sources & evidence

ORD record
ord-c436de7edd024b27b76ba05e17871347
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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