Potassium Carbonate → 1-(4-{4-[7-amino-2-(6-fluoro-1H-indol-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone

HRID 389509Notes

Reaction equation

HRID 389509 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:12]2[CH:13]=[N:14][N:15]([CH:17]3[CH2:22][CH2:21][N:20]([C:23](=[O:25])[CH3:24])[CH2:19][CH2:18]3)[CH:16]=2)=[C:6]2[CH:10]=[C:9](Cl)[O:8][C:7]=12.O1CCOCC1.[F:32][C:33]1[CH:41]=[C:40]2[C:36]([C:37](B3OC(C)(C)C(C)(C)O3)=[CH:38][N:39]2[Si](C(C)C)(C(C)C)C(C)C)=[CH:35][CH:34]=1.C(=O)([O-])[O-].[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:12]2[CH:13]=[N:14][N:15]([CH:17]3[CH2:22][CH2:21][N:20]([C:23](=[O:25])[CH3:24])[CH2:19][CH2:18]3)[CH:16]=2)=[C:6]2[CH:10]=[C:9]([C:37]3[C:36]4[C:40](=[CH:41][C:33]([F:32])=[CH:34][CH:35]=4)[NH:39][CH:38]=3)[O:8][C:7]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 66759397HCID 66759397, compoundHCID 667609686-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1-(triisopropylsilyl)-indole

Product 1

HCID 667605771-(4-{4-[7-amino-2-(6-fluoro-1H-indol-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanoneYield 28%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

To a nitrogen degassed solution of 1-{4-[4-(7-amino-2-chloro-furo[2,3-c]pyridin-4-yl)-pyrazol-1-yl]-piperidin-1-yl}ethanone (0.050 g, 0.14 mmol) in 4:1 1,4-dioxane:water (10 mL) was added 6-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-triisopropylsilanyl-1H-indole (0.060 g, 0.143 mmol), potassium carbonate (0.047 g, 0.34 mmol), dichlorobis(triphenylphosphine)palladium (16 mg, 0.023 mmol). The mixture was heated at reflux for 3 h, then cooled to room temperature and concentrated. The residue was suspended in water and extracted with ethyl acetate (3×50 mL). The combined organic fractions were washed with water (15 mL), dried, and evaporated. Purification by flash chromatography (5% MeOH:DCM) afforded 18 mg (28%) of the title compound as a solid. 1H NMR (300 MHz, CDCl3): δ 1.99-2.14 (m, 2H), 2.17 (s, 3H), 2.24-2.34 (m, 2H), 2.81 (t, J=12 Hz, 1H), 3.29 (m, 1H), 4.02 (d, J=14.7 Hz, 1H), 4.40-4.48 (m, 1H), 4.78 (br. s, 2H), 4.78-4.82 (m, 1H), 6.97 (s, 1H), 7.07 (dt, J=9 Hz, 2.4 Hz, 1H), 7.16 (dd, J=9 Hz, 2.4 Hz, 1H), 7.70 (s, 1H), 7.78 (d, J=2.7 Hz, 1H), 7.87 (s, 1H), 7.92-7.97 (m, 2H), 8.94 (brs, 1H); MS (ESI): 459 [M+H]+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 h
  3. concentrationconcentrated
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe combined organic fractions were washed with water (15 mL)
  6. customdried
  7. customevaporated
  8. customPurification by flash chromatography (5% MeOH:DCM)

Sources & evidence

ORD record
ord-c1ab2a6216b742b4a21cdc600dc659e5
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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