Cesium carbonate → [2-Methoxy-6-(6-methoxy-pyridin-3-yl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine

HRID 216143Notes

Reaction equation

HRID 216143 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][N:24]=1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.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>[CH3:9][O:8][C:6]1[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:3]=[C:2]([C:26]2[CH:25]=[N:24][C:23]([O:22][CH3:21])=[CH:28][CH:27]=2)[N:7]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 57636025(6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxyphenyl)-ethyl]amine

Product 1

HCID 57636121[2-Methoxy-6-(6-methoxy-pyridin-3-yl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amineYield 100%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine (600 mg, 2.04 mmol), 2-methoxy-5-pyridyl-boronic acid (469 mg, 3.06 mmol, prepared according to the procedure described in J. Org. Chem., 2002, 67, 7541), and Cs2CO3 (1.66 g, 5.11 mmol) in ethylene glycol dimethyl ether (8 mL) and water (2 mL), at room temperature, is degassed with argon gas for 5 minutes and treated with tetrakis(triphenylphosphine)palladium (0) (118 mg, 0.1 mmol). The mixture is heated at 85° C. for 5 hours, diluted with water (50 mL), and extracted twice with EtOAc (50 mL). The combined extracts are dried over magnesium sulfate, filtered and evaporated. The residue is subjected to chromatography on silica gel eluting with a mixture of EtOAc and heptane (1:1, v/v) affording [2-methoxy-6-(6-methoxy-pyridin-3-yl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine [0.75 g, 100%, Example 35(o)] as an oil. LCMS: RT=2.74 minutes, MS: 367 (M+H). 1H NMR (300 MHz, CDCl3): □08.78 (1H, d, J=2.1 Hz), 8.21 (1H, dd, J=8.7, 2.4 Hz), 7.16 (2H, d, J=8.4 Hz), 6.88 (1H, dd, J=8.7, 2.4 Hz), 6.82 (2H, d, J=8.4 Hz), 6.3 (1H, s), 4.95 (1H, brs), 4.03 (3H, s), 4.02 (3H, s), 3.82 (3H, s), 3.72-3.63 (2H, m), 2.92 (2H, t, J=6.9 Hz). IC50=1.7 nM

Workup

  1. customprepared
  2. extractionextracted twice with EtOAc (50 mL)
  3. dry with materialThe combined extracts are dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. additionThe residue is subjected to chromatography on silica gel eluting with a mixture of EtOAc and heptane (1:1

Sources & evidence

ORD record
ord-658e038618f6424bae184bc844f3e873
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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