ethyl 3-((1-(1-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate → ethyl 3-((1-(1-(2-aminoethyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

HRID 522783Notes

Reaction equation

HRID 522783 reaction equation
C(OC([NH:8][CH2:9][CH2:10][N:11]1[CH:15]=[C:14]([N:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([Cl:26])[C:23]=3[F:25])[C:18]([S:27][C:28]3[C:29]([F:39])=[C:30]([CH:36]=[CH:37][CH:38]=3)[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:17]2[CH:40]2[CH2:42][CH2:41]2)[CH:13]=[N:12]1)=O)(C)(C)C>Cl.O1CCOCC1>[NH2:8][CH2:9][CH2:10][N:11]1[CH:15]=[C:14]([N:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([Cl:26])[C:23]=3[F:25])[C:18]([S:27][C:28]3[C:29]([F:39])=[C:30]([CH:36]=[CH:37][CH:38]=3)[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:17]2[CH:40]2[CH2:42][CH2:41]2)[CH:13]=[N:12]1

Participants

4

Reactant 1

HCID 118874671ethyl 3-((1-(1-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 1

HCID 118104181ethyl 3-((1-(1-(2-aminoethyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoateYield 81%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of compound 3 (200 mg, 0.32 mmol) in 4.0 M HCl in 1,4-dioxane (5 mL) under inert atmosphere was stirred at 0° C.-RT for 2 h. The volatiles were removed under reduced pressure. 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 afford 4 (130 mg, 81%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.24 (s, 1H), 7.82 (s, 1H), 7.60 (t, J=6.8 Hz, 1H), 7.22-7.11 (m, 3H), 6.84 (t, J=6.8 Hz, 1H), 4.33 (q, 2H), 4.17 (t, J=6.0 Hz, 2H), 2.98 (t, J=6.0 Hz, 2H), 1.84-1.80 (m, 3H), 1.32 (t, J=7.2 Hz, 3H), 0.92-0.91 (m, 2H), 0.84-0.82 (m, 2H); MS: m/z 517.6 (M+H+).

Workup

  1. customThe volatiles were removed under reduced pressure
  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

Sources & evidence

ORD record
ord-acde23274f8d4dada926bc9cbd53a1c8
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

Loading…