Cesium carbonate → Benzo[1,3]dioxol-4-yl-(2-chloro-5-methyl-pyrimidin-4-yl)-amine

HRID 491193

Reaction equation

HRID 491193 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH3:9])=[CH:4][N:3]=1.Br[C:11]1[C:19]2[O:18][CH2:17][O:16][C:15]=2[CH:14]=[CH:13][CH:12]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(Cl)Cl.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]>[O:16]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:8][C:6]3[C:5]([CH3:9])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)[C:19]=2[O:18][CH2:17]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27761894-Bromo-1,3-benzodioxoleHCID 43021752-Chloro-5-methylpyrimidin-4-amine

Product 1

HCID 57674946Benzo[1,3]dioxol-4-yl-(2-chloro-5-methyl-pyrimidin-4-yl)-amineYield 39.1%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 2-chloro-5-methyl-pyrimidin-4-ylamine (1.4 g, 9.7 mmol), 4-bromo-benzo[1,3]dioxole (2.0 g, 10 mmol), Pd2(dba)3 (0.80 g, 0.87 mmol), Xantphos (1.0 g, 1.7 mmol) and cesium carbonate (6.3 g, 19 mmol) was suspended in dioxane (40 mL) and heated at reflux under the argon atmosphere for 5 h. The reaction mixture was cooled to room temperature and diluted with DCM (30 mL). The mixture was filtered and the filtrate concentrated in vacuo. The residue was purified by flash chromatography on silica gel (hexanes to 50% EtOAc/hexanes) to afford the title compound (1.0 g, 39%) as a white solid. 1H NMR (500 MHz, DMSO-d6): δ 2.13 (s, 3H), 5.99 (s, 2H), 6.80-6.90 (m, 3H), 8.01 (s, 1H), 8.92 (s, 1H). MS (ES+): m/z 264 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureat reflux under the argon atmosphere for 5 h
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel (hexanes to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-75cc7d16f37149ddac111f8ad4152a83
Source dataset
uspto-grants-2009_05
Patent number
US07528143B2

Linked notes

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