Diisopropylethylamine → HCID 44540155, compound

HRID 244732Notes

Reaction equation

HRID 244732 reaction equation
[F:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][N:5]([CH3:7])[CH:6]=1.FC1C=NN(C)C=1C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH:54]1[C:62]2[C:57](=[C:58]([C:63]3[CH:64]=[C:65]([NH2:72])[C:66]4[CH:67]=[N:68][NH:69][C:70]=4[CH:71]=3)[CH:59]=[CH:60][CH:61]=2)[CH:56]=[CH:55]1>CN(C=O)C.CO>[F:1][C:2]1[C:3]([C:8]([NH:72][C:65]2[CH:64]=[C:63]([C:58]3[CH:59]=[CH:60][CH:61]=[C:62]4[C:57]=3[CH:56]=[CH:55][NH:54]4)[CH:71]=[C:70]3[C:66]=2[CH:67]=[N:68][NH:69]3)=[O:10])=[N:4][N:5]([CH3:7])[CH:6]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 553023704-fluoro-1-methyl-1H-pyrazole-3-carboxylic acidHCID 582680196-(1H-indol-4-yl)-1H-indazol-4-amineHCID 583563891198437-10-3

Product 1

HCID 44540155HCID 44540155, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

A mixture 4-fluoro-1-methyl-1H-pyrazole-3-carboxylic acid and 4-fluoro-1-methyl-1H-pyrazole-5-carboxylic acid (45:55) (580 mg, 20% W/W), HATU (306 mg), and DIPEA (0.422 ml) in DMF (3 ml) was stirred at RT for 10 min. 6-(1H-Indol-4-yl)-1H-indazol-4-amine (100 mg) in DMF (3 ml) was then added and the mixture was stirred at RT overnight. The reaction mixture was added to a 20 g aminopropyl SPE cartridge which had been preconditioned with methanol. The reaction mixture was allowed to remain on the cartridge for 3 h before being eluted with methanol (4 column volumes) and then 10%-triethylamine in methanol (6 column volumes). The appropriate fractions were evaporated to give a brown oil which was partitioned between ethyl acetate (25 ml) and water (5 ml). The phases were separated and the organic phase was dried over anhydrous sodium sulphate and evaporated to a brown oil. This was dissolved in ethyl acetate (10 ml) and pre-adsorbed on silica (1.2 g) which was then added to the top of a 20 g silica SPE cartridge. The cartridge was eluted with a gradient of 0-100% ethyl acetate in cyclohexane over 60 min to give the title compound (65 mg) as a buff-coloured solid.

Workup

  1. additionThe reaction mixture was added to a 20 g aminopropyl SPE cartridge which
  2. waitto remain on the cartridge for 3 h
  3. washbefore being eluted with methanol (4 column volumes)
  4. customThe appropriate fractions were evaporated
  5. customto give a brown oil which
  6. customwas partitioned between ethyl acetate (25 ml) and water (5 ml)
  7. customThe phases were separated
  8. dry with materialthe organic phase was dried over anhydrous sodium sulphate
  9. customevaporated to a brown oil
  10. dissolutionThis was dissolved in ethyl acetate (10 ml) and pre-adsorbed on silica (1.2 g) which
  11. additionwas then added to the top of a 20 g silica SPE cartridge
  12. washThe cartridge was eluted with a gradient of 0-100% ethyl acetate in cyclohexane over 60 min

Sources & evidence

ORD record
ord-b3f8709fd8ec41db99cd7df9b1782cff
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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