Cesium carbonate → 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

HRID 522785Notes

Reaction equation

HRID 522785 reaction equation
N[CH2:2][CH2:3][N:4]1[CH:8]=[C:7]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([Cl:19])[C:16]=3[F:18])[C:11]([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:10]2[CH:33]2[CH2:35][CH2:34]2)[CH:6]=[N:5]1.C([O-])([O-])=O.[Cs+].[Cs+].BrCC[CH2:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47]>CN(C=O)C>[C:49]([O:48][C:46](=[O:47])[CH2:45][CH2:2][CH2:3][N:4]1[CH:8]=[C:7]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([Cl:19])[C:16]=3[F:18])[C:11]([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:10]2[CH:33]2[CH2:35][CH2:34]2)[CH:6]=[N:5]1)([CH3:52])([CH3:51])[CH3:50]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2757253tert-Butyl 4-bromobutanoateHCID 118104181ethyl 3-((1-(1-(2-aminoethyl)-1H-pyrazol-4-yl)-6-chloro-2-cyclopropyl-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 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-fluorobenzoateYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of indole 1 (Example 11, Step 3; 200 mg, 0.42 mmol) in DMF (5 mL) under inert atmosphere were added Cs2CO3 (206 mg, 0.63 mmol) and tert-butyl 4-bromobutanoate (141 mg, 0.63 mmol) at RT and stirred for 16 h. The mixture was diluted with ice cold water (20 mL) and extracted with EtOAc (3×30 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to obtain the crude. This was purified (silica gel chromatography; 20% EtOAc/hexanes) to afford compound 2 (180 mg, 70%) as a pale brown oil. 1H NMR (400 MHz, CDCl3): δ 7.67 (s, 1H), 7.64 (s, 1H), 7.63-7.60 (m, 1H), 7.18 (d, J=8.4 Hz, 1H), 7.10-7.06 (m, 1H), 6.93 (t, J=8.0 Hz, 1H), 6.77 (t, J=7.6 Hz, 1H), 4.41 (q, 2H), 4.28 (t, J=6.8 Hz, 2H), 2.28-2.19 (m, 4H), 1.74-1.66 (m, 1H), 1.46 (s, 9H), 1.41 (t, J=7.2 Hz, 3H), 1.06-1.02 (m, 2H), 0.89-0.84 (m, 2H); LC-MS (ESI): m/z 618.6 (M+H+).

Workup

  1. extractionextracted with EtOAc (3×30 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 chromatography; 20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2ce0701bb5104bd789e385cdc7e2fec2
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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