Triethylamine → 2-Chloro-4-(6-dimethylaminopyridin-3-yl)pyrimidine

HRID 1027972Notes

Reaction equation

HRID 1027972 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH3:9][N:10]([CH3:20])[C:11]1[N:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(N(CC)CC)C>ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd].C(Cl)Cl.COCCOC>[Cl:1][C:2]1[N:7]=[C:6]([C:14]2[CH:15]=[N:16][C:11]([N:10]([CH3:20])[CH3:9])=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 775312,4-DichloropyrimidineHCID 27632716-(Dimethylamino)pyridine-3-boronic acid

Product 1

HCID 579113532-Chloro-4-(6-dimethylaminopyridin-3-yl)pyrimidineYield 71.2%

Reagents, catalysts & solvents 2

HCID 178478476HCID 178478476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A flask containing 2,4-dichloropyrimidine (0.5 g, 3.35 mmol), [6-(dimethylamino)pyridin-3-yl]boronic acid (0.61 g, 3.67 mmol) and DME (10 mL) was purged with N2 for 10 min. Dichloro[1,1′-bis(diphenylphosphino)]ferrocene-palladium CH2Cl2 adduct (0.37 g, 0.50 mmol) and triethylamine (0.85 g, 1.17 mL, 8.33 mmol) were added successively to the flask with continuous bubbling of N2 including 5 min. post addition of the reagents. The reaction mixture was stirred and heated at 90° C. for 5 h. Reaction progress was monitored by TLC (silica gel). The reaction mixture was concentrated and diluted with water, wherein a tan solid formed. The solid was filtered, dried and purified by silica gel column chromatography using 50% EtOAc/hexanes as eluent to provide 2-chloro-4-(6-dimethylaminopyridin-3-yl)pyrimidine as a white solid (0.56 g, 71%); 1H NMR (DMSO-d6): δ 8.91 (s, 1H), 8.60 (d, 1H, J=5.3 Hz), 8.20 (dd, 1H, J=2.3 and 9.1 Hz), 7.95 (d, 1H, J=5.3 Hz), 6.74 (d, 1H, J=9.1 Hz), 3.11 (s, 3H). LCMS: purity: 98%; MS (m/e): 235 (MH+).

Workup

  1. customwas purged with N2 for 10 min
  2. customwith continuous bubbling of N2 including 5 min. post addition of the reagents
  3. customReaction progress
  4. concentrationThe reaction mixture was concentrated
  5. additiondiluted with water, wherein a tan solid
  6. customformed
  7. filtrationThe solid was filtered
  8. customdried
  9. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-5c3f24a2cec94203a6794c52c2849484
Source dataset
uspto-grants-2014_05
Patent number
US08735418B2

Reaction notes

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