1,2-Dimethoxyethane → HCID 11584210, compound

HRID 216227Notes

Reaction equation

HRID 216227 reaction equation
[C:1]([O-:4])([O-])=[O:2].[Cs+].[Cs+].Cl[C:8]1[N:13]=[C:12]([O:14][CH3:15])[N:11]=[C:10]([NH:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[Cl:26])[CH:9]=1.CO[CH2:29][CH2:30][O:31][CH3:32]>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>[Cl:26][C:20]1[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:19]=1[CH2:18][CH2:17][NH:16][C:10]1[N:11]=[C:12]([O:14][CH3:15])[N:13]=[C:8]([C:21]2[CH:20]=[C:19]([C:18]3([C:1]([OH:4])=[O:2])[CH2:17][CH2:32][O:31][CH2:30][CH2:29]3)[CH:24]=[CH:23][CH:22]=2)[CH:9]=1

Participants

6

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamine

Product 1

HCID 11584210HCID 11584210, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Cs2CO3 solution (1.5 g, 4.6 mmol in 15 mL of water) is added to a stirred solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine (0.61 g, 1.84 mmol) and 3-(4-tetrahydro-pyran-4-carboxylic acid)-phenylboronic acid (0.6 g, 2.4 mmol) in 1,2-dimethoxyethane (45 mL). The mixture is degassed over nitrogen for 10 minutes, tetrakis(triphenylphosphine)palladium (0) (64 mg, 0.03 mmol) is added and the reaction mixture is refluxed at 90° C. overnight. The reaction is cooled to room temperature, diluted with water (150 mL), filtered over a pad of celite and the volatiles are removed in vacuo. The aqueous solution is slowly acidified (pH 4-5, 0.1N HCl) with vigorous stirring, which is continued for 2 hours. The formed precipitate is suction filtered and air dried to afford 4-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid [605 mg, Example 80(a)]. LCMS: Rt=2.26 minutes, MS: 502. 504 (M+H), H′ NMR [300 MHz, (CD3SO)2SO]: □12.75 (1H, b) 8 (1H, s), 7.8 (1H, b), 7.55 (2H, b), 7.45 (2H, s), 7.35 (2H, s), 6.55 (1H, s), 3.85 (3H, s), 3.82 (2H, m), 3.5 (4H, m), 2.95 (2H, t, J=2 Hz), 2.4 (2H, m), 1.85 (2H, m). IC50=0.05 nM

Workup

  1. customThe mixture is degassed over nitrogen for 10 minutes
  2. temperatureThe reaction is cooled to room temperature
  3. filtrationfiltered over a pad of celite
  4. customthe volatiles are removed in vacuo
  5. filtrationfiltered
  6. customair dried

Sources & evidence

ORD record
ord-9c48e9797b51460da2a81be9ad723de7
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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