Water → (R)-3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide

HRID 546207Notes

Reaction equation

HRID 546207 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])[C@@H:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[C:25]([O:33][CH3:34])[CH:24]=2)[CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:10]1)(C)(C)C.O1CCCC1.O>Cl.C(O)(=O)C>[CH:18]1([CH2:17][C@H:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[C:25]([O:33][CH3:34])[CH:24]=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])[CH2:19][CH2:20][CH2:21][CH2:22]1

Participants

6

Reactant 3

HCID 962WaterHCID 8028TetrahydrofuranHCID 67193508(R)-N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide

Product 1

HCID 67189250(R)-3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamideYield 31%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
25 °C

Procedure

In a round bottom flask was placed (R)—N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide (14 mg, 0.03 mmol), tetrahydrofuran (2 mL), water (0.5 mL) and acetic acid (2 mL). It was stirred at 25° C. for 2 h and after this time concentrated hydrochloric acid (2 drops) was added and the reaction was complete in 20 min. The reaction was worked up and then purified on a Biotage Flash chromatography system (12M column, silica gel, 10% methanol/ethyl acetate) to afford (R)-3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide (4 mg, 31%): [α]30589=−40.0° (c=0.10, methanol); ES-HRMS m/e calcd for C21H29N3O5S (M+H)+ 436.1901, observed 436.1902; 1H NMR (300 MHz, DMSO-d6) δ 1.13 (m, 2H, CH2), 1.36-1.83 (m, 8H, 4×CH2), 2.13 (m, 1H, CH), 3.20 (s, 3H, SO2CH3), 3.66 (m, 2 H, OCH2), 3.86 (m, 1H, ArCHCO), 3.95 (s, 3H, OCH3), 3.99 (t, J=5.7 Hz, 2 H, NCH2), 4.83 (t, J=5.3 Hz, 1H, OH), 6.41 (d, J=2.2 Hz, 1H, Ar), 7.14 (dd, Jm=1.2 Hz, Jo=8.2 Hz, 1H, Ar), 7.27 (d, Jm=1.2 Hz, 1H, Ar), 7.53 (d, J=2.2 Hz, 1H, Ar), 7.73 (d, Jo=8.2 Hz, 1H, Ar), 10.72 (s, 1H, NH).

Workup

  1. customIn a round bottom flask was placed
  2. waitthe reaction was complete in 20 min
  3. custompurified on a Biotage Flash chromatography system (12M column, silica gel, 10% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-6ff1993c2aa34a4c8969040d7befc05c
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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