Sodium Hydroxide → HCID 54576679, compound

HRID 2202775Notes

Reaction equation

HRID 2202775 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[S:10][CH:9]=[C:8]([C:11]([OH:13])=O)[CH:7]=2)[CH:3]=[N:2]1.[F:14][C:15]1([C:23]2[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][N:24]=2)[CH2:21][CH:20]2[NH:22][CH:17]([CH2:18][CH2:19]2)[CH2:16]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[OH-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[F:14][C:15]1([C:23]2[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][N:24]=2)[CH2:16][CH:17]2[N:22]([C:11]([C:8]3[CH:7]=[C:6]([C:4]4[CH:5]=[N:1][NH:2][CH:3]=4)[S:10][CH:9]=3)=[O:13])[CH:20]([CH2:19][CH2:18]2)[CH2:21]1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581101935-(1H-Pyrazol-4-YL)thiophene-3-carboxylic acidHCID 67468365HCID 67468365, compound

Product 1

HCID 54576679HCID 54576679, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(1H-Pyrazol-4-yl)-thiophene-3-carboxylic acid (0.04 g, 0.2 mmol) and 3-fluoro-3-(3-methyl-pyridin-2-yl)-8-aza-bicyclo[3.2.1]octane (PA Mixture) (0.058 g, 0.2 mmol) were dissolved in DMF (3 mL). HATU (0.093 g, 0.24 mmol) and diisopropylethylamine (0.144 mL, 0.89 mmol) were added and the resulting mixture was stirred for 1 hour. Aqueous sodium hydroxide (1 N, 3 mL) was added and the mixture stirred for 0.5 hours. The mixture was diluted with ethyl acetate and washed with brine, dried over magnesium sulphate, filtered and the solvent evaporated under vacuum. The residues were purified by HPLC on a C18 cartridge, eluting with 40%-70% methanol/water with 0.1% formic acid. The fractions containing the desired products were concentrated under vacuum and further lyophilised from methanol and water to give the title compounds.

Workup

  1. stirringthe mixture stirred for 0.5 hours
  2. washwashed with brine
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated under vacuum
  6. customThe residues were purified by HPLC on a C18 cartridge
  7. washeluting with 40%-70% methanol/water with 0.1% formic acid
  8. additionThe fractions containing the desired products
  9. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-8acbd0b7af0c47a89316d13b8ea12fca
Source dataset
uspto-grants-2016_06
Patent number
US09365564B2

Reaction notes

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