Diisopropylethylamine → HCID 178426298, compound

HRID 1616052Notes

Reaction equation

HRID 1616052 reaction equation
[CH3:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:35][C:36]1[C:44]2[C:43]([NH2:45])=[CH:42][C:41]([C:46]3[CH:54]=[CH:53][CH:52]=[C:51]4[C:47]=3[CH:48]=[CH:49][NH:50]4)=[CH:40][C:39]=2[NH:38][N:37]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH3:4].[CH3:8][OH:9].[F:35][C:36]1[C:44]2[C:39](=[CH:40][C:41]([C:46]3[CH:54]=[CH:53][CH:52]=[C:51]4[C:47]=3[CH:48]=[CH:49][NH:50]4)=[CH:42][C:43]=2[NH:45][C:8]([C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)=[O:10])[NH:38][N:37]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2687573-Methylpicolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178507273HCID 178507273, compound

Product 2

HCID 21705897Ammonia methanolHCID 178426298HCID 178426298, compoundYield 13.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

To 3-Methyl-2-pyridinecarboxylic acid (0.032 g, 0.234 mmol) in DMF (0.5 ml) was added HATU (0.089 g, 0.234 mmol) and the solution stirred for 10 min at 20° C. To this was then added a solution of 3-fluoro-6-(1H-indol-4-yl)-1H-indazol-4-amine (0.052 g, 0.195 mmol) in DMF (0.5 ml), followed by DIPEA (0.068 ml, 0.391 mmol) and the top was placed on the vial which had been pierced with a needle. The mixture was stirred at 20° C. for 66 hours then loaded directly onto a dry 1 g NH2 cartridge, left for 2 hours then eluted with methanol (2.5 column vols). Upon standing for 20 hours at 20° C., a solid precipitated from the orange solution which was filtered off and dried. The solid was triturated with methanol (2×2 ml) then blown to dryness and loaded onto a 500 mg SCX pre-rinsed with methanol. Elution with methanol (3 column vols) then 2M NH3/MeOH (3 column vols) and concentration of the basic fractions by blow down afforded the title compound (6 mg).

Workup

  1. stirringThe mixture was stirred at 20° C. for 66 hours
  2. waitleft for 2 hours
  3. washthen eluted with methanol (2.5 column vols)
  4. waitUpon standing for 20 hours at 20° C.
  5. customa solid precipitated from the orange solution which
  6. filtrationwas filtered off
  7. customdried
  8. customThe solid was triturated with methanol (2×2 ml)
  9. washpre-rinsed with methanol
  10. washElution with methanol (3 column vols)

Sources & evidence

ORD record
ord-fffd4132a77f4dc98301d614649637f9
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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