HCID 66899380, compound → HCID 44464798, compound

HRID 2381460Notes

Reaction equation

HRID 2381460 reaction equation
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:40])[CH:16]([N:24]2[C:29](=[O:30])[CH:28]=[C:27]([O:31][C:32]3[C:37]([F:38])=[CH:36][CH:35]=[CH:34][C:33]=3[F:39])[CH:26]=[N:25]2)[CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:10]1)(C)(C)C>C(O)C.Cl.C(OCC)(=O)C>[F:38][C:37]1[CH:36]=[CH:35][CH:34]=[C:33]([F:39])[C:32]=1[O:31][C:27]1[CH:26]=[N:25][N:24]([CH:16]([CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][OH:6])[N:10]=2)=[O:40])[C:29](=[O:30])[CH:28]=1

Participants

5

Reactant 1

HCID 66899380HCID 66899380, compound

Product 1

HCID 44464798HCID 44464798, compoundYield 68.4%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (540.6 mg, 0.89 mmol) in ethanol (4.5 mL) at 25° C. was treated with concentrated aqueous hydrochloric acid (9 drops). The reaction was stirred at 25° C. overnight. After this time, the reaction was diluted with ethyl acetate (150 mL) and was washed with a saturated aqueous sodium bicarbonate solution (2×100 mL), water (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were dried over magnesium sulfate, filtered, rinsed and then concentrated in vacuo. Silica gel column chromatography (AnaLogix 80 g, 1-10% methanol/methylene chloride) afforded 2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (298 mg, 68%) as a white solid; ES+-HRMS m/e calcd for C23H25N5O5F2 [M+H+] 490.1897 found 490.1895. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.12-1.34 (m, 2H) 1.34-1.46 (m, 1H) 1.46-1.59 (m, 2H) 1.90 (ddd, J=13.6, 9.0, 4.3 Hz, 1H) 2.12-2.28 (m, 1H) 3.08-3.29 (m, 2H) 3.69 (q, J=5.5 Hz, 2H) 3.74-3.89 (m, 2H) 4.02 (t, J=5.5 Hz, 2H) 4.86 (t, J=5.5 Hz, 1H) 5.54 (dd, J=11.0, 4.3 Hz, 1H) 6.04 (d, J=2.7 Hz, 1H) 6.36 (d, J=2.1 Hz, 1H) 7.32-7.43 (m, 2H) 7.43-7.53 (m, 1H) 7.56 (d, J=2.1 Hz, 1H) 8.29 (d, J=2.7 Hz, 1H) 10.84 (s, 1H).

Workup

  1. washwas washed with a saturated aqueous sodium bicarbonate solution (2×100 mL), water (1×100 mL)
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. washrinsed
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-685e0e52124a4fa2ae5c8d4939639faf
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

Loading…