6-Bromopyridine-2-carbaldehyde → 6-(2-{[(2-Methylphenyl)amino]methyl}-1-naphthyl)pyridine-2-carbaldehyde

HRID 1944822Notes

Reaction equation

HRID 1944822 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH3:10][C:11]1[CH:37]=[CH:36][CH:35]=[CH:34][C:12]=1[NH:13][CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]=1B1OC(C)(C)C(C)(C)O1.ClCCl.C(OCC)(=O)C>CO.O.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:10][C:11]1[CH:37]=[CH:36][CH:35]=[CH:34][C:12]=1[NH:13][CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]=1[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 27570096-Bromopyridine-2-carbaldehydeHCID 21226138Dichloromethane ethylacetateHCID 667958502-Methyl-N-{[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthyl]methyl}aniline

Product 1

HCID 866633926-(2-{[(2-Methylphenyl)amino]methyl}-1-naphthyl)pyridine-2-carbaldehyde

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 28.4 g (99.0 mmol) of Na2CO3(H2O)10 in a mixture of 150 ml of methanol and 580 ml of water was added to a mixture of 7.38 g (39.7 mmol) of 6-bromopyridine-2-carbaldehyde, 14.8 g (39.7 mmol) of 2-methyl-N-{ [1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthyl]methyl}aniline and 2.29 g (2.00 mmol) of Pd(PPh3)4 in 720 ml of toluene by vigorous stirring at room temperature. The resulting mixture was stirred at 80° C. for 12 h. Further on, this mixture was cooled to room temperature, the organic layer was separated, dried over MgSO4, and then evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 um; eluent: dichloromethane-ethyl acetate=100:1 and then 20:1). Yield 10.7 g (76%). Anal. calc. for C24H20N2O: C, 81.79; H, 5.72; N, 7.95. Found: C, 81.91; H, 5.80; N, 7.81. 1H NMR (CDCl3): 10.10 (s, 1H, CHO), 8.01-8.05 (m, 2H, 3,4-H in Py), 7.96 (d, J=8.6 Hz, 1H, 4-H in naphthyl), 7.90 (m, 1H, 8-H in naphthyl), 7.68-7.70 (m, 2H, 5-H in Py and 3-H in naphthyl), 7.60 (m, 1H, 7-H in naphthyl), 7.41 (m, 1H, 6-H in naphthyl), 7.81 (m, 1H, 5-H in naphthyl), 7.03 (m, 2H, 3,5-H in Ph), 6.63 (m, 1H, 4-H in Ph), 6.50 (m, 1H, 6-H in Ph), 4.22 (m, 2H, CH2N), 3.93 (br. s, 1H, NH), 2.10 (s, 3H, Me).

Workup

  1. stirringThe resulting mixture was stirred at 80° C. for 12 h
  2. temperatureFurther on, this mixture was cooled to room temperature
  3. customthe organic layer was separated
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe product was isolated by flash chromatography on silica gel 60 (40-63 um

Sources & evidence

ORD record
ord-599f6f511c064490add20ce01d6da1d8
Source dataset
uspto-grants-2013_03
Patent number
US08394902B2

Reaction notes

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