Hydrochloric Acid → Ethyl 6-(hydroxymethyl)-2-iodo-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxylate

HRID 920843Notes

Reaction equation

HRID 920843 reaction equation
C(OC([N:8]1[CH:12]([CH2:13][N:14]2[C:18]([C:19](OCC)=[O:20])=[C:17]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:16]([I:29])=[N:15]2)[CH2:11][O:10]C1(C)C)=O)(C)(C)C.Cl>O1CCOCC1>[OH:10][CH2:11][CH:12]1[CH2:13][N:14]2[N:15]=[C:16]([I:29])[C:17]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:18]2[C:19](=[O:20])[NH:8]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118062571Diethyl 1-((3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl)methyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

Product 1

HCID 118062830Ethyl 6-(hydroxymethyl)-2-iodo-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxylateYield 73.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of Intermediate 351A (3.3 g, 5.99 mmol) in dioxane (10 mL) was added 4 M HCl in dioxane (5 mL, 5.99 mmol) and the resulting reaction mixture was stirred at RT for 3 h. The reaction mixture was concentrated and the crude product was basified with a 10% aqueous solution of sodium bicarbonate and extracted with EtOAc (3×100 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated slowly (2 to 3 h) using a rotary evaporator at 60° C. to obtain Intermediate 351B (1.6 g, 67.4%) as a white solid. MS(ES): m/z=366 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.43 (d, J=3.0 Hz, 1H), 5.14 (t, J=5.5 Hz, 1H), 4.46-4.41 (m, 1H), 4.37-4.30 (m, 1H), 4.25 (q, J=7.0 Hz, 2H), 3.84-3.75 (m, 1H), 3.54-3.47 (m, 1H), 3.36 (s, 1H), 1.28 (t, J=7.0 Hz, 3H).

Workup

  1. customthe resulting reaction mixture
  2. concentrationThe reaction mixture was concentrated
  3. extractionextracted with EtOAc (3×100 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated slowly (2 to 3 h)
  7. customa rotary evaporator at 60° C.

Sources & evidence

ORD record
ord-b135869b8490493e95fbe9630045ec0c
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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