Sodium hydride → HCID 71253953, compound

HRID 1775100Notes

Reaction equation

HRID 1775100 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:15]([N:16]4[CH2:20][CH2:19][NH:18][C:17]4=[O:21])=[N:14][N:13]([CH:22]4[CH2:27][CH2:26][CH2:25][CH2:24][O:23]4)[C:10]3=[CH:11][N:12]=2)[CH:2]=1.[H-].[Na+].[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][CH:40]([CH2:43]Br)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31]>CN(C)C=O>[O:21]=[C:17]1[N:16]([C:15]2[C:9]3[C:10](=[CH:11][N:12]=[C:7]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH:8]=3)[N:13]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[N:14]=2)[CH2:20][CH2:19][N:18]1[CH2:43][CH:40]1[CH2:41][CH2:42][N:37]([C:35]([O:34][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:36])[CH2:38][CH2:39]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 71253874HCID 71253874, compound

Product 1

HCID 71253953HCID 71253953, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)imidazolidin-2-one (0.120 g, 0.329 mmol) dissolved in N,N-Dimethylformamide (3.43 mL) and cooled to 0° C. was added NaH in Oil (6:4, Sodium hydride:Mineral Oil, 26.3 mg). The reaction mixture was stirred at RT for 30 mins then cooled to 0° C. 4-bromomethyl-piperidine-1-carboxylic acid tert-butyl ester (0.183 g, 0.659 mmol) was added. The reaction was stirred at RT for 18 hr. The mixture was quenched with H2O then extracted with EtOAc. The organic layers was dried, filtered, and concentrated to give tert-butyl 4-((2-oxo-3-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)imidazolidin-1-yl)methyl)piperidine-1-carboxylate which was dissolved in 4.0 M of Hydrogen chloride in 1,4-Dioxane (6.00 mL) and 1,4-Dioxane (3.00 mL, 38.4 mmol;) was stirred at RT 18 h. The reaction was concentrated and submitted for rHPLC purification to give 296 (11.6 mg, 9.3% yield). ESI MS m/z=378.2 (M+1). 1H NMR (400 MHz, DMSO) δ 9.17 (s, 1H), 9.03 (s, 1H), 8.78 (s, 1H), 8.55 (d, J=4.7 Hz, 1H), 8.30 (d, J=8.0 Hz, 1H), 7.50 (dd, J=8.0, 4.7 Hz, 1H), 4.03-3.93 (m, 2H), 3.65-3.56 (m, 2H), 3.11 (d, J=7.2 Hz, 2H), 2.92 (d, J=12.0 Hz, 2H), 2.42 (d, J=10.9 Hz, 1H), 1.79-1.67 (m, 1H), 1.59 (d, J=11.8 Hz, 2H), 1.05 (dd, J=21.5, 9.9 Hz, 2H)

Workup

  1. temperaturethen cooled to 0° C
  2. stirringThe reaction was stirred at RT for 18 hr
  3. customThe mixture was quenched with H2O
  4. extractionthen extracted with EtOAc
  5. customThe organic layers was dried
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f6184b62d5ab435fa7e0e5da7d1299c9
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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