Dimethylacetamide → ethyl 3-((6-chloro-2-cyano-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

HRID 522756Notes

Reaction equation

HRID 522756 reaction equation
Br[C:2]1[N:3]([C:24]2[CH:25]=[N:26][N:27]([CH2:29][CH2:30][CH3:31])[CH:28]=2)[C:4]2[C:9]([C:10]=1[S:11][C:12]1[CH:13]=[C:14]([CH:20]=[CH:21][CH:22]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:8][CH:7]=[C:6]([Cl:23])[CH:5]=2.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C[C:75]([N:77](C)C)=O>O.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:23][C:6]1[CH:5]=[C:4]2[C:9]([C:10]([S:11][C:12]3[CH:13]=[C:14]([CH:20]=[CH:21][CH:22]=3)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:2]([C:75]#[N:77])[N:3]2[C:24]2[CH:25]=[N:26][N:27]([CH2:29][CH2:30][CH3:31])[CH:28]=2)=[CH:8][CH:7]=1

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 118094237ethyl 3-((2-bromo-6-chloro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoate

Product 1

HCID 118094311ethyl 3-((6-chloro-2-cyano-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)benzoateYield 33%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of compound 4 (200 mg, 0.38 mmol) in DMA (20 mL) under inert atmosphere were added zinc powder (5.02 mg, 0.07 mmol), ZnCN2 (67.8 mg, 0.58 mmol), xantphos (89.5 mg, 0.15 mmol), Pd2(dba)3 (70.85 mg, 0.07 mmol) at RT; heated to 120° C. under microwave for 30 min. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 10-15% EtOAc/Hexanes to afford compound 5 (60 mg, 33%) as an off-white solid. 1H NMR (500 MHz, CDCl3): δ 7.99 (s, 1H), 7.87 (d, J=7.5 Hz, 1H), 7.78 (s, 2H), 7.54 (d, J=8.5 Hz, 1H), 7.42-7.27 (m, 3H), 7.24-7.22 (m, 1H), 4.36 (q, J=7.0 Hz, 2H), 4.21 (t, J=7.5 Hz, 2H), 2.02-1.98 (m, 2H), 1.36 (t, J=7.0 Hz, 3H), 1.01 (t, J=7.5 Hz, 3H); LC-MS (ESI): 92.5%; m/z 465 (M+H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.92 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. customafter completion of the reaction
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude
  7. customThis was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a029630f116243d9a87281b749012f7f
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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