Diisopropylethylamine → HCID 52916802, compound

HRID 2172971Notes

Reaction equation

HRID 2172971 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[N:14][CH:15]=[C:16]([C:17]([OH:19])=O)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.FC(F)(F)C(O)=O.[Br:60][C:61]1[CH:66]=[C:65]([C:67]2([NH2:70])[CH2:69][CH2:68]2)[CH:64]=[CH:63][N:62]=1>CN(C=O)C>[Br:60][C:61]1[CH:66]=[C:65]([C:67]2([NH:70][C:17]([C:16]3[C:11]4[CH:10]=[N:9][N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[C:12]=4[CH:13]=[N:14][CH:15]=3)=[O:19])[CH2:68][CH2:69]2)[CH:64]=[CH:63][N:62]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592781371-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acidHCID 86672757HCID 86672757, compound

Product 1

HCID 52916802HCID 52916802, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (0.120 g, 0.467 mmol) in DMF (2 mL) is added HATU (186 mg, 0.490 mmol). After 30 minutes, N,N-diisopropylethylamine (325 μL, 1.87 mmol) and 1-(2-bromo-pyridin-4-yl)-cyclopropylamine-trifluoroacetic acid salt (223 mg, 0.507 mmol) are added, and the reaction mixture became homogeneous. After 18 hours, the mixture is concentrated in vacuo, reconstituted in ethyl acetate (50 mL) and washed with 1N sodium hydroxide (3×50 mL). The organic layer is washed with saturated aqueous ammonium chloride (2×50 mL), saturated aqueous sodium bicarbonate (50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue is twice purified by silica gel chromatography eluting with a gradient of 0-10% methanol in methylene chloride to afford the title compound as a solid.

Workup

  1. waitAfter 18 hours
  2. concentrationthe mixture is concentrated in vacuo
  3. washwashed with 1N sodium hydroxide (3×50 mL)
  4. washThe organic layer is washed with saturated aqueous ammonium chloride (2×50 mL), saturated aqueous sodium bicarbonate (50 mL), brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is twice purified by silica gel chromatography
  9. washeluting with a gradient of 0-10% methanol in methylene chloride

Sources & evidence

ORD record
ord-c3abf09e8c8d47429c20a385deb62fc0
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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