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

HRID 2171296Notes

Reaction equation

HRID 2171296 reaction equation
[F:1][C:2]1[C:12]([SH:13])=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].C1C(=O)N(Cl)C(=O)C1.[Cl:22][C:23]1[C:31]([F:32])=[C:30]2[C:26]([CH:27]=[C:28]([CH:40]3[CH2:42][CH2:41]3)[N:29]2[C:33]2[CH:34]=[N:35][N:36]([CH2:38][CH3:39])[CH:37]=2)=[CH:25][CH:24]=1>C(Cl)Cl.O>[Cl:22][C:23]1[C:31]([F:32])=[C:30]2[C:26]([C:27]([S:13][C:12]3[C:2]([F:1])=[C:3]([CH:9]=[CH:10][CH:11]=3)[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[C:28]([CH:40]3[CH2:42][CH2:41]3)[N:29]2[C:33]2[CH:34]=[N:35][N:36]([CH2:38][CH3:39])[CH:37]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 31398ChlorosuccinimideHCID 66765235Ethyl 2-fluoro-3-mercaptobenzoateHCID 1181041966-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indole

Product 1

HCID 118094209ethyl 3-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoateYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of ethyl 2-fluoro-3-mercaptobenzoate 6 (2.8 g, 14.0 mmol) in CH2Cl2 (30 mL) under inert atmosphere was added NCS (1.9 g, 14.0 mmol) at RT and allowed to stir for 2 h. To this, compound 5 (3.9 g, 12.8 mmol) in CH2Cl2 (10 mL) was added at RT and stirred for 16 h. After completion of the reaction by TLC, the reaction mixture was diluted with water (100 mL) and extracted with CH2Cl2 (2×80 mL). The combined organic extracts were washed with water (2×200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified by triturating with n-pentane (2×50 mL) to afford 7 (5.2 g, 81%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3): δ 7.66-7.7.60 (m, 3H), 7.18 (d, J=8.4 Hz, 1H), 7.08 (dd, J=8.4, 6.5 Hz, 1H), 6.93 (t, J=8.4 Hz, 1H), 6.79-6.75 (m, 1H), 4.40 (q, J=7.2 Hz, 2H), 4.26 (q, J=7.6 Hz, 2H), 1.74-1.68 (m, 1H), 1.56 (t, J=7.2 Hz, 3H), 1.41 (t, J=7.6 Hz, 3H), 1.08-1.04 (m, 2H), 0.89-0.84 (m, 2H); MS (ESI): m/z 502.5 (M+H+); HPLC: 97.5%; (column: Acquity BEH C-18 (50×2.1 mm, 1.7μ); RT 3.44 min; ACN: 0.025% TFA (aq); 0.5 mL/min.

Workup

  1. stirringstirred for 16 h
  2. customAfter completion of the reaction by TLC
  3. extractionextracted with CH2Cl2 (2×80 mL)
  4. washThe combined organic extracts were washed with water (2×200 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto obtain the crude
  9. customThe crude was purified
  10. customby triturating with n-pentane (2×50 mL)

Sources & evidence

ORD record
ord-5083b423241b4bf68a58519ffaed1d3c
Source dataset
uspto-grants-2015_06
Patent number
US09051320B1

Reaction notes

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