Potassium Phosphate, Tribasic → HCID 117778620, compound

HRID 2206551Notes

Reaction equation

HRID 2206551 reaction equation
[CH:1]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11](Cl)[CH:12]=2)[C:7]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:28])[NH:21][C:22]([CH3:27])=[CH:23][C:24]=2[O:25][CH3:26])=[O:16])=[C:6]1[CH3:29])([CH2:3][CH3:4])[CH3:2].[N:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=1.C1(C(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.ClCCl.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].O1CCOCC1>[CH:1]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:32]3[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=3)[CH:12]=2)[C:7]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:28])[NH:21][C:22]([CH3:27])=[CH:23][C:24]=2[O:25][CH3:26])=[O:16])=[C:6]1[CH3:29])([CH2:3][CH3:4])[CH3:2]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 137109TricyclohexylmethaneHCID 27343783-Pyridinylboronic acidHCID 89741790HCID 89741790, compound2×

Product 1

HCID 117778620HCID 117778620, compoundYield 5.8%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (±)-1-(sec-butyl)-6-chloro-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1H-indole-3-carboxamide (Compound 185) (50 mg, 0.12 mmol), pyridine-3-ylboronic acid (22 mg, 0.18 mmol), tricyclohexylmethane (7 mg, 0.024 umol), K3PO4 (120 mg, 0.60 mmol), Tris(dibenzylideneacetone)dipalladium(0)(10 mg), water (1 mL) and 1,4-dioxane (4 mL) was stirred under N2 at 100° C. for 16 h. The reaction was then allowed to cool to rt and the mixture was diluted with water and dichloromethane, the aqueous layer was extracted with dichloromethane. The organic layers were dried with Na2SO4 and evaporated. The residue was purified by preparative-HPLC (Instrument: Gilson 215; Column: Gemini C18 10 u 150*25 mm; Mobile phase A: Water (0.0225% HCl v/v); Mobile phase B: Acetonitrile (neutral); Gradient: 42-62 (B %); Flowrate: 25 ml/min) The collected fractions were combined and lyophilized to give 1-(sec-butyl)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-6-(pyridine-3-yl)-1H-indole-3-carboxamide as a yellow solid (3.2 mg, yield 5.7%). LCMS (M+H+) m/z: calcd 458.23. found 459.0. 1H NMR (400 MHz, CD3OD): δ9.25 (s, 1H), 8.98 (d, J=8.4, 1H), 8.80 (d, J=5.6, 1H), 8.18 (t, J=5.6, 1H), 8.05 (s, 1H), 7.97 (d, J=8.0, 1H), 7.60 (d, J=8.4, 1H), 6.86 (s, 1H), 4.64 (m, 1H), 4.62 (s, 2H), 4.13 (s, 3H), 2.73 (s, 3H), 2.53 (s, 3H), 2.30 (m, 1H), 2.03-2.10 (m, 1H), 1.71 (d, J=6.8, 3H), 0.77 (t, J=7.6, 3H).

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane
  2. dry with materialThe organic layers were dried with Na2SO4
  3. customevaporated
  4. customThe residue was purified by preparative-HPLC (Instrument

Sources & evidence

ORD record
ord-f8c18e645f5e4ec492a458fdbf8cba55
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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