Cesium carbonate → 3-{6-[2-(3,4-Difluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenol

HRID 216209Notes

Reaction equation

HRID 216209 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]([F:19])=[C:15]([F:20])[CH:14]=2)[CH:3]=1.C([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)#N.C([O-])([O-])=[O:33].[Cs+].[Cs+]>O.COCCOC.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>[F:20][C:15]1[CH:14]=[C:13]([CH2:12][CH2:11][NH:10][C:4]2[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:23]3[CH:24]=[C:25]([OH:33])[CH:26]=[CH:27][CH:28]=3)[CH:3]=2)[CH:18]=[CH:17][C:16]=1[F:19]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27343253-Cyanophenylboronic acidHCID 86240123(6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(3,4-difluoro-phenyl)-ethyl]-amine

Product 1

HCID 690666123-{6-[2-(3,4-Difluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenolYield 57.7%

Reagents, catalysts & solvents 3

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

Procedure

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(3,4-difluoro-phenyl)-ethyl]-amine (1.6 g), 3-cyano-phenylboronic acid (1.5 g), Cs2CO3 (8.3 g) and tetrakis(triphenylphosphine)palladium (0) (45 mg) in water (8 mL) and DME (32 mL) is heated at 90° C. for 16 hours. The solution is poured into water and extracted with EtOAc (2×200 mL). The combined extract is dried over sodium sulfate, filtered, evaporated in vacuo and chromatographed on silica gel eluting with EtOAc to afford 3-{6-[2-(3,4-difluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenol (1.1 g). MS: 379 (M+H); 1H NMR (300 MHz, CDCl3) □8.3 (1H, s); 8.2 (1H, d, J=5.1 Hz); 7.9 (1H, d (J=5.1 Hz)); 7.6 (1H, t); 7-7.2 (4H, m); 6.4 (1H, s); 5 (1H, m); 3.95 (3H, s); 3.7 (2H, t); 3 (2H, t).

Workup

  1. extractionextracted with EtOAc (2×200 mL)
  2. extractionThe combined extract
  3. dry with materialis dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customchromatographed on silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-837b772d50874d8cb69951b334269724
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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