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

HRID 522781Notes

Reaction equation

HRID 522781 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:20][C:21]3[C:22]([F:32])=[C:23]([CH:29]=[CH:30][CH:31]=3)[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:7][N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18]C)[CH:16]=2)=[CH:4][CH:3]=1.[C:33]([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:40][CH2:41]O.[OH2:43]>CN(C=O)C>[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:20][C:21]3[C:22]([F:32])=[C:23]([CH:29]=[CH:30][CH:31]=3)[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:7]([CH:41]3[CH2:40][CH2:33]3)[N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH2:18][OH:43])[CH:16]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 108982-BromoethanolHCID 118094307ethyl 3-((6-chloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 1

HCID 118104210ethyl 3-((6-chloro-2-cyclopropyl-7-fluoro-1-(1-(2-hydroxvethyl)-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)-2-fluorobenzoateYield 19%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of indole 1 (Example 11, Step 3; 480 mg, 1.01 mmol) in DMF (10 mL) under inert atmosphere were added Cs2CO3 (1.32 g, 4.05 mmol) and 2-bromoethan-1-ol (152 mg, 1.27 mmol) at RT and stirred for 16 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the crude. This was purified (silica gel; 55% EtOAc/hexanes) to obtain compound 2 (100 mg, 19%) as a colorless syrup. 1H NMR (400 MHz, CDCl3): δ 7.72 (d, J=6.8 Hz, 2H), 7.62 (dt, J=8.0 Hz, 1.6 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 7.10-7.07 (m, 1H), 6.94 (t, J=8.0 Hz, 1H), 6.78 (dt, J=8.0, 1.6 Hz, 1H), 4.41 (q, 2H), 4.36-4.34 (m, 2H), 4.10 (t, J=4.8 Hz, 2H), 2.72 (br s, 1H), 1.74-1.67 (m, 1H), 1.41 (t, J=7.2 Hz, 3H), 1.08-1.04 (m, 2H), 0.90-0.85 (m, 2H); LC-MS: m/z 518.7 (M+H+).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the crude
  6. customThis was purified (silica gel; 55% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6d1087030522463ca12960595d624fce
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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