Ethanol → 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide

HRID 546131Notes

Reaction equation

HRID 546131 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:35])[CH:16]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[C:26]([Cl:34])[CH: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>[Cl:34][C:26]1[CH:25]=[C: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:35])[CH:29]=[CH:28][C:27]=1[S:30]([CH3:33])(=[O:32])=[O:31]

Participants

5

Reactant 2

HCID 702EthanolHCID 67188252N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide

Product 1

HCID 671902242-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamideYield 90.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

In a flask containing N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionamide (150 mg, 0.26 mmol) was added ethanol (5 mL) and concentrated hydrochloric acid (three drops) and was stirred at 25° C. for 30 minutes. It was then diluted with ethyl acetate (50 mL) and washed with water (1×20 mL) and saturated aqueous brine solution (1×20 mL). The organic layer was then dried over sodium sulfate and absorbed onto silica gel (2 g) and purified on Biotage Flash purification system (40S column, silica gel, 5% methanol/ethyl acetate) which afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (107 mg, 89%) as a white foam: ES-HRMS m/e calcd for C20H26N3O5SCl (M+H)+ 456.1355, observed 456.1354; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-1.27 (m, 2H, CH2), 1.29-1.42 (m, 1H, CH of CH2), 1.49-1.70 (m, 3H, CH of CH2 and CH2), 2.00-2.14 (m, 1H, CH), 3.20 (m, 2H, OCH2), 3.34 (s, 3H, SO2CH3), 3.67 (q, J=5.5 Hz, 2H, OCH2), 3.75-3.86 (m, 2H, OCH2), 3.95-4.08 (m, 3H, CH and NCH2), 4.83 (t, J=5.3 Hz, 1H, OH), 6.41 (d, J=2.3 Hz, 1H, Ar), 7.54 (d, J=2.3 Hz, 1H, Ar), 7.60 (dd, Jo=8.2 Hz, Jm=1.6 Hz, 1H, Ar), 7.71 (d, Jm=1.6 Hz, 1H, Ar), 8.01 (d, Jo=8.2 Hz, 1H, Ar), 10.81 (s, 1H, NH).

Workup

  1. washwashed with water (1×20 mL) and saturated aqueous brine solution (1×20 mL)
  2. dry with materialThe organic layer was then dried over sodium sulfate
  3. customabsorbed onto silica gel (2 g)
  4. custompurified on Biotage Flash purification system (40S column, silica gel, 5% methanol/ethyl acetate) which

Sources & evidence

ORD record
ord-8882c360a6e5418db3ad7364150f52a7
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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