Potassium Phosphate, Tribasic → HCID 68757708, compound

HRID 1465241Notes

Reaction equation

HRID 1465241 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22](B(O)O)[CH:21]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.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>[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:2]2[CH:10]=[CH:9][C:8]3[NH:7][C:6]4[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C:5]=4[C:4]=3[CH:3]=2)[CH:21]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 12629892HCID 12629892, compound

Product 1

HCID 68757708HCID 68757708, compoundYield 64.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

Preparation of the title compound was carried out according to General Method 7. A mixture of ethyl 8-bromo-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (See Example 7) (100 mg, 0.3 mmol), pyridine-3-boronic acid (76 mg, 0.62 mmol) and K3PO4 (120 mg, 0.57 mmol) in DMF:H2O (2:1, 3 ml) was purged with nitrogen for 30 minutes. PdCl2(PPh3)2 (25 mg, 0.04 mmol) was added and the reaction was heated at 100° C. for 4 h. The contents were concentrated in vacuo and the crude product was purified by silica gel chromatography (230-400 mesh) using ethyl acetate-hexane gradient to obtain 62 mg of ethyl 3,4-dihydro-8-(pyridin-3-yl)-1H-pyrido[4,3-b]indole-2(5H)-carboxylate. This intermediate (25 mg, 0.078 mmol), 2-methyl-5-vinylpyridine (0.120 ml, 1 mmol) and NaH (10 mg, 60% dispersion in oil, 0.02 mmol) were heated in DMSO (0.3 ml) at 100° C. for 48 h, after which methanol was added and the contents were concentrated to dryness. The resulting crude product was purified by silica gel chromatography (100-200 mesh or 230-400 mesh) using methanol-dichloromethane gradient to obtain 7 mg of 3,4-dihydro-5-(2-(6-methylpyridin-3-yl)-8-(pyridin-3-yl)-1H-pyrido[4,3-b]indole-2(5H)-carboxylate.

Workup

  1. customwas purged with nitrogen for 30 minutes
  2. concentrationThe contents were concentrated in vacuo
  3. customthe crude product was purified by silica gel chromatography (230-400 mesh)

Sources & evidence

ORD record
ord-06e7c60358754b1f935b32ebcd5adafd
Source dataset
uspto-grants-2015_04
Patent number
US08999978B2

Reaction notes

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