Hydrochloric Acid → HCID 72199095, compound

HRID 588742Notes

Reaction equation

HRID 588742 reaction equation
Cl.[CH3:2][C@H:3]1[N:8]([CH2:9][C:10]([F:13])([F:12])[F:11])[C:7](=[O:14])[C@@H:6]([NH:15][S:16]([C:19]2[CH:20]=[C:21]3[CH2:44][C@@:26]4([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[N:28](COCC[Si](C)(C)C)[C:27]4=[O:43])[CH2:25][C:22]3=[N:23][CH:24]=2)(=[O:18])=[O:17])[CH2:5][C@H:4]1[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>O1CCOCC1>[CH3:2][C@H:3]1[N:8]([CH2:9][C:10]([F:13])([F:12])[F:11])[C:7](=[O:14])[C@@H:6]([NH:15][S:16]([C:19]2[CH:20]=[C:21]3[CH2:44][C@@:26]4([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[NH:28][C:27]4=[O:43])[CH2:25][C:22]3=[N:23][CH:24]=2)(=[O:18])=[O:17])[CH2:5][C@H:4]1[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 131734442HCID 131734442, compound

Product 1

HCID 72199095HCID 72199095, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of HCl in dioxane (4 M, 0.7 mL, 2.8 mmol) was added to a solution of (S)—N-((3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl)-2′-oxo-1′-((2-(trimethylsilyl)ethoxy)methyl)-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-sulfonamide (0.027 g, 0.038 mmol) in dioxane (0.5 mL) pre-cooled to 0° C. The mixture was gradually warmed to ambient temperature, then heated at 60° C. for 22 h. The reaction mixture was concentrated in vacuo, and the residue was purified by reverse-phase HPLC (C18 column), eluting with 30% MeOH in water (0.1% TFA used as a modifier) initially, grading to 100% MeOH over 30 min with a flow rate of 15 mL/min to furnish the title compound. MS: m/z=586.2 (M+1). 1H NMR (400 MHz, CD3OD) δ 8.92 (s, 1H), 8.22 (s, 1H), 8.11 (d, 1H, J=4.3 Hz), 7.42-7.34 (m, 3H), 7.32-7.23 (m, 3H), 6.93 (dd, 1H, J=7.4, 5.4 Hz), 4.88 (obscured m, 1H), 4.62 (dq, 1H, J=15.2, 9.4 Hz), 4.30 (dd, 1H, J=11.7, 7.2 Hz), 3.84 (quintet, 1H, J=6.0 Hz), 3.68-3.57 (m, 3H), 3.36-3.29 (obscured m, 2H), 2.65-2.52 (m, 1H), 2.45-2.36 (m, 1H), 0.98 (d, 3H, J=6.5 Hz).

Workup

  1. temperatureThe mixture was gradually warmed to ambient temperature
  2. temperatureheated at 60° C. for 22 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was purified by reverse-phase HPLC (C18 column)
  5. washeluting with 30% MeOH in water (0.1% TFA

Sources & evidence

ORD record
ord-3bc45890f9c04379bbe78f2ca2e26709
Source dataset
uspto-grants-2016_01
Patent number
US09227972B2

Reaction notes

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