Ammonium fluoride → 1-cyclopropyl-3-((3-(4-hydroxybutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one

HRID 80632

Reaction equation

HRID 80632 reaction equation
[Si]([O:8][CH2:9][CH2:10]/[CH:11]=[CH:12]/[C:13]1[N:17]2[CH:18]=[CH:19][N:20]=[CH:21][C:16]2=[N:15][C:14]=1[CH2:22][N:23]1[C:27]2[CH:28]=[N:29][CH:30]=[CH:31][C:26]=2[N:25]([CH:32]2[CH2:34][CH2:33]2)[C:24]1=[O:35])(C(C)(C)C)(C)C.[F-].[NH4+]>CO.[Pd]>[CH:32]1([N:25]2[C:26]3[CH:31]=[CH:30][N:29]=[CH:28][C:27]=3[N:23]([CH2:22][C:14]3[N:15]=[C:16]4[CH:21]=[N:20][CH:19]=[CH:18][N:17]4[C:13]=3[CH2:12][CH2:11][CH2:10][CH2:9][OH:8])[C:24]2=[O:35])[CH2:33][CH2:34]1

Participants

5

Reactant 2

HCID 25516Ammonium fluorideHCID 86704031(E)-3-((3-(4-(tert-butyldimethylsilyloxy)but-1-enyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one

Product 1

HCID 574102501-cyclopropyl-3-((3-(4-hydroxybutyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1H-imidazo[4,5-c]pyridin-2(3H)-oneYield 87%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (E)-3-((3-(4-(tert-butyldimethylsilyloxy)but-1-enyl)imidazo[1,2-a]pyrazin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one 11-a (480 mg, 0.978 mmole) and Pd/C 10% (52 mg, 0.05 eq) in MeOH (20 mL) was hydrogenated for 2 h. The reaction mixture was then filtered over dicalite and concentrated to dryness. The resulting white solid (480 mg, 84%) was used directly in the next step. It was redissolved in MeOH and ammonium fluoride (39 mg, 1.1 eq) was added. The reaction mixture was then heated at 60° C. overnight. After concentration, the crude was purified by Prep HPLC on (RP Vydac Denali C18-10 μm, 250 g, 5 cm), with the following mobile phase (0.25% NH4HCO3 solution in water, CH3CN), to give the targeted product P17 in 87% yield (320 mg). m/z=491 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.82-0.94 (m, 2H), 0.99-1.10 (m, 2H), 1.36-1.46 (m, 2H), 1.46-1.59 (m, 2H), 2.96 (tdd, J=6.96, 6.96, 3.64, 3.51 Hz, 1H), 3.08 (t, J=7.53 Hz, 2 H), 3.34-3.43 (m, 2H), 4.38 (t, J=5.14 Hz, 1H), 5.22 (s, 2H), 7.23 (dd, J=5.27, 0.75 Hz, 1H), 7.88 (d, J=4.52 Hz, 1H), 8.22 (d, J=5.27 Hz, 1H), 8.40 (s, 1H), 8.44 (dd, J=4.64, 1.38 Hz, 1H), 8.97 (d, J=1.51 Hz, 1H).

Workup

  1. filtrationThe reaction mixture was then filtered over dicalite
  2. concentrationconcentrated to dryness
  3. dissolutionIt was redissolved in MeOH
  4. concentrationAfter concentration
  5. customthe crude was purified by Prep HPLC on (RP Vydac Denali C18-10 μm, 250 g, 5 cm), with the following mobile phase (0.25% NH4HCO3 solution in water, CH3CN)
  6. customto give the targeted product P17 in 87% yield (320 mg)

Sources & evidence

ORD record
ord-a9c3d403fff64a98a3aaed3720c1747c
Source dataset
uspto-grants-2014_09
Patent number
US08846672B2

Linked notes

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