ethyl 3-((1-(1-(4-(tert-butoxy)-4-oxobutyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate → 4-(4-(6-chloro-2-cyclopropyl-3-((3-(ethoxycarbonyl)-2-fluorophenyl) thio)-7-fluoro-1H-indol-1-yl)-1H-pyrazol-1-yl)butanoic acid

HRID 522786Notes

Reaction equation

HRID 522786 reaction equation
C([O:5][C:6](=[O:42])[CH2:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13]([N:15]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([Cl:25])[C:22]=3[F:24])[C:17]([S:26][C:27]3[C:28]([F:38])=[C:29]([CH:35]=[CH:36][CH:37]=3)[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:16]2[CH:39]2[CH2:41][CH2:40]2)[CH:12]=[N:11]1)(C)(C)C>Cl.O1CCOCC1>[Cl:25][C:21]1[C:22]([F:24])=[C:23]2[C:18]([C:17]([S:26][C:27]3[CH:37]=[CH:36][CH:35]=[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:28]=3[F:38])=[C:16]([CH:39]3[CH2:40][CH2:41]3)[N:15]2[C:13]2[CH:12]=[N:11][N:10]([CH2:9][CH2:8][CH2:7][C:6]([OH:42])=[O:5])[CH:14]=2)=[CH:19][CH:20]=1

Participants

4

Reactant 1

HCID 118094304ethyl 3-((1-(1-(4-(tert-butoxy)-4-oxobutyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 1

HCID 1181041884-(4-(6-chloro-2-cyclopropyl-3-((3-(ethoxycarbonyl)-2-fluorophenyl) thio)-7-fluoro-1H-indol-1-yl)-1H-pyrazol-1-yl)butanoic acidYield 56%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of compound 2 (100 mg, 0.29 mmol) in 4.0 M HCl in 1,4-dioxane (2 mL) under inert atmosphere was stirred at 0° C.-RT for 16 h. The volatiles were removed in vacuo and the residue was diluted with water (5 mL), basified with aq. NaHCO3 (5 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the crude. This was purified by acid-base treatment to afford 3 (50 mg, 56%) as a white solid. 1H NMR (500 MHz, DMSO-d6): 12.75 (br s, 1H), 8.24 (s, 1H), 7.82 (s, 1H), 7.59 (t, J=7.0 Hz, 1H), 7.22-7.10 (m, 3H), 6.84 (t, J=7.5 Hz, 1H), 4.33 (q, 2H), 4.22 (t, J=7.0 Hz, 2H), 2.21 (t, J=7.5 Hz, 2H), 2.06-2.03 (m, 2H), 1.81-1.78 (m, 1H), 1.32 (t, J=7.0 Hz, 3H), 0.89-0.88 (m, 2H), 0.82-0.81 (m, 2H); MS: m/z 560.7 (M+H+).

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with water (5 mL)
  3. extractionextracted with EtOAc (2×20 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude
  8. customThis was purified by acid-base treatment

Sources & evidence

ORD record
ord-ada5fa78e68f4416a09d409b0584a200
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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