Diisopropylethylamine → 1-(2,2-Dimethylpropyl)-5-[2-(isoxazol-3-ylcarbonyl)-2-azabicyclo[2.2.2]-oct-5-en-5-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629861Notes

Reaction equation

HRID 629861 reaction equation
[CH:1]12[CH2:24][CH2:23][CH:4]([C:5]([C:7]3[N:12]=[C:11]4[N:13]([CH3:22])[C:14](=[O:21])[N:15]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:10]4=[CH:9][CH:8]=3)=[CH:6]1)[CH2:3][NH:2]2.[O:25]1[CH:29]=[CH:28][C:27]([C:30](O)=[O:31])=[N:26]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCOCC1>[CH3:18][C:17]([CH3:19])([CH3:20])[CH2:16][N:15]1[C:10]2[C:11](=[N:12][C:7]([C:5]3[CH:4]4[CH2:23][CH2:24][CH:1]([CH:6]=3)[N:2]([C:30]([C:27]3[CH:28]=[CH:29][O:25][N:26]=3)=[O:31])[CH2:3]4)=[CH:8][CH:9]=2)[N:13]([CH3:22])[C:14]1=[O:21]

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 112864533-Isoxazolecarboxylic acidHCID 71135233HCID 71135233, compound

Product 1

HCID 711367461-(2,2-Dimethylpropyl)-5-[2-(isoxazol-3-ylcarbonyl)-2-azabicyclo[2.2.2]-oct-5-en-5-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

5-(2-Azabicyclo[2.2.2]oct-5-en-5-yl)-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (2-5, 291 mg, 0.90 mmol, 1.0 equiv), isoxazole-3-carboxylic acid (2-6, 151 mg, 1.4 mmol, 1.5 equiv), DIPEA (0.47 mL, 2.7 mmol, 3.0 equiv) and HATU (510 mg, 1.4 mmol, 1.5 equiv) were added to anhydrous 1,4-dioxane (9 mL). After stirring for 10 min at room temperature, LCMS showed consumption of starting material. Purification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O) provided 2-7 as a white solid. MS m/z (M+H): calculated=422.2187; observed=422.2189. 1H NMR δ (ppm)(CHCl3-d): 8.40 (1H, dd, J=27.77, 1.66 Hz), 7.22-7.17 (1H, m), 7.12 (1H, dd, J=8.11, 1.50 Hz), 6.97 (1H, m), 6.70 (1H, dd, J=11.92, 1.66 Hz), 5.55-5.52 (0.4H, m), 5.42-5.38 (0.6H, m), 3.95 (0.4H, m), 3.88 (1H, m), 3.62 (2.6H, m), 3.53 (0.4H, m), 3.47 (3H, d, J=3.86 Hz), 3.36 (0.6H, d, J=12.39 Hz), 2.21-2.11 (1H, m), 1.91-1.80 (1H, m), 1.61-1.52 (2H, m) 0.99 (9H, d, J=1.91 Hz). (Mixture of rotamers at RT).

Workup

  1. customconsumption of starting material
  2. customPurification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O)

Sources & evidence

ORD record
ord-c338b552f5f1431baec426221571c293
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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