Cesium carbonate → N-(2-methyl-5-nitropyridin-3-yl)-4-(pyridin-3-yl)pyrimidin-2-amine

HRID 2174641

Reaction equation

HRID 2174641 reaction equation
Br[C:2]1[C:3]([CH3:11])=[N:4][CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH2:24])[N:19]=2)[CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+].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>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:11][C:3]1[C:2]([NH:24][C:20]2[N:19]=[C:18]([C:14]3[CH:13]=[N:12][CH:17]=[CH:16][CH:15]=3)[CH:23]=[CH:22][N:21]=2)=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 124505824-(Pyridin-3-yl)pyrimidin-2-amineHCID 184588223-Bromo-2-methyl-5-nitropyridine

Product 1

HCID 46910559N-(2-methyl-5-nitropyridin-3-yl)-4-(pyridin-3-yl)pyrimidin-2-amineYield 50.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 3-bromo-2-methyl-5-nitro-pyridine (380 mg, 1.75 mmol) and 4-pyridin-3-yl-pyrimidin-2-ylamine (250 mg, 1.45 mmol) in dry toluene (20 mL) were added Cs2CO3 (710 mg, 2.18 mmol), Pd2(dba)3 (26 mg, 0.028 mmol) and Xantphos (50 mg, 0.086 mmol). The mixture was evacuated and purged with N2 (3 cycles), heated to 90° C. under N2 for 16 h. After completion (monitored by TLC), the reaction mixture was cooled to rt, diluted with EtOAc and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2) using CH2Cl2-MeOH (98:2) to afford product (225 mg, 50%). 1H NMR (200 MHz, CDCl3): δ 2.76 (s, 3H), 7.23 (m, 1H), 7.38 (d, J=6.0 Hz, 1H), 7.51 (m, 1H), 8.51 (m, 1H), 8.63 (d, J=6.0 Hz, 1H), 8.77 (m, 1H), 9.04 (d, J=2.0 Hz, 1H), 9.28 (d, J=2.0 Hz, 1H), 9.77 (d, J=2.0 Hz, 1H); Mass [M+H]+: 309.

Workup

  1. customThe mixture was evacuated
  2. custompurged with N2 (3 cycles)
  3. temperatureAfter completion (monitored by TLC), the reaction mixture was cooled to rt
  4. additiondiluted with EtOAc
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by column chromatography (SiO2)

Sources & evidence

ORD record
ord-4939f1cea86c47cf8234de3723e13c1a
Source dataset
uspto-grants-2015_06
Patent number
US09062023B2

Linked notes

Loading…