Potassium Carbonate → HCID 86698602, compound

HRID 1054598Notes

Reaction equation

HRID 1054598 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].CC1(C)COB([C:21]2[CH:26]=[CH:25][C:24]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[CH:23][C:22]=2[F:32])OC1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([CH:12]=[O:13])=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:21]1[CH:26]=[CH:25][C:24]([C:27]2([OH:31])[CH2:28][CH2:29][CH2:30]2)=[CH:23][C:22]=1[F:32]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehydeHCID 866986011-[4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-3-fluorophenyl]cyclobutanol

Product 1

HCID 86698602HCID 86698602, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 5-bromo-6-chloro-1H-indole-3-carbaldehyde (150 mg, 0.44 mmol), 1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-fluorophenyl]cyclobutanol (181 mg, 0.652 mmol), 2 M aqueous potassium carbonate (0.87 mL, 1.74 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (18 mg, 0.022 mmol) in ethanol (4 mL) was sealed in a reaction vessel and heated thermally to 130° C. for 3 hours. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine and dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using flash chromatography eluting with heptanes/ethyl acetate (0:100 to 60:40) to give the title compound (57 mg, 58%). 1H NMR (500 MHz, DMSO-d6) δ 12.18-12.38 (m, 1 H), 9.95 (s, 1 H), 8.40 (s, 1H), 8.04 (s, 1H), 7.73 (s, 1H), 7.34-7.50 (m, 3H), 5.68 (s, 1H), 2.40-2.47 (m, 2H), 2.21-2.38 (m, 2H), 1.90-1.99 (m, 1H), 1.68-1.81 (m, 1H).

Workup

  1. customwas sealed in a reaction vessel
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified
  8. washeluting with heptanes/ethyl acetate (0:100 to 60:40)

Sources & evidence

ORD record
ord-92c644a0f21c4ca8b5fd437a257a23f4
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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