6-Bromopyridine-2-carbaldehyde → HCID 86663391, compound

HRID 1944812Notes

Reaction equation

HRID 1944812 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[C:10]([NH:14][CH2:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]=1B1OC(C)(C)C(C)(C)O1)([CH3:13])([CH3:12])[CH3:11]>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>[C:10]([NH:14][CH2:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]=1[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1)([CH3:13])([CH3:11])[CH3:12]

Participants

7

Reactant 2

HCID 27570096-Bromopyridine-2-carbaldehydeHCID 66795972HCID 66795972, compound

Product 1

HCID 86663391HCID 86663391, compound

Reagents, catalysts & solvents 4

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

Procedure

A solution of 37.0 g (129 mmol) of Na2CO3(H2O)10 in a mixture of 200 ml of methanol and 600 ml of water was added to a mixture of 9.58 g (51.5 mmol) of 6-bromopyridine-2-carbaldehyde, 17.5 g (51.5 mmol) of tert-butyl{[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthyl]methyl}amine and 3.00 g (2.60 mmol) of Pd(PPh3)4 in 1000 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 and evaporated to dryness. The residue was dissolved in 700 ml of 2 M HCl, and this solution was extracted with 3×200 ml of toluene. To the aqueous layer a solution of K2CO3 was added to pH 9, and the product was extracted with 2×300 ml of dichloromethane. This organic extract was dried over MgSO4 and then evaporated to dryness. Yield 15.2 g (46%). Anal. calc. for C21H22N2O: C, 79.21; H, 6.96; N, 8.80. Found: C, 79.30; H, 7.14; N, 8.65. 1H NMR (CDCl3): 10.18 (s, 1H, CHO), 8.07 (m, 1H, 3-H in Py), 8.02 (m, 1H, 4-H in Py), 7.92 (m, 1H, 8-H in naphthyl), 7.88 (m, 1H, 5-H in naphthyl), 7.71 (m, 1H, 5-H in Py), 7.66 (d, J=8.3 Hz, 1H, 4-H in naphthyl), 7.45 (m, 1H, 7-H in naphthyl), 7.36 (m, 1H, 6-H in naphthyl), 7.28 (d, J=8.3 Hz, 1H, 3-H in naphthyl), 3.53 (m, 2H, CH2N), 1.55 (br. s, 1H, NH), 0.94 (s, 9H, tBu).

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. customevaporated to dryness
  5. dissolutionThe residue was dissolved in 700 ml of 2 M HCl
  6. extractionthis solution was extracted with 3×200 ml of toluene
  7. additionTo the aqueous layer a solution of K2CO3 was added to pH 9
  8. extractionthe product was extracted with 2×300 ml of dichloromethane
  9. extractionThis organic extract
  10. dry with materialwas dried over MgSO4
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-ffb95520d6fd4455b9a97ae4d0aa749b
Source dataset
uspto-grants-2013_03
Patent number
US08394902B2

Reaction notes

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