1,2-Dimethoxyethane → HCID 53316574, compound

HRID 216274Notes

Reaction equation

HRID 216274 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]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([CH3:33])([CH3:32])[C:29]([OH:31])=[O:30])=[CH:24][C:23]=1B1OC(C)(C)C(C)(C)O1.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>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[CH2:12][CH2:11][NH:10][C:4]1[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:27]2[CH:26]=[C:25]([C:28]([CH3:33])([CH3:32])[C:29]([OH:31])=[O:30])[CH:24]=[CH:23][C:22]=2[F:21])[CH:3]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamineHCID 69074227HCID 69074227, compound

Product 1

HCID 53316574HCID 53316574, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Procedure

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichlorophenyl)-ethyl]amine (0.24 g), 2-[4-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-methyl-propionic acid (0.4 g), Cs2CO3 (1.01 g) and tetrakis(triphenylphosphine)palladium (0) (100 mg) in water (20 mL)/DME (80 mL) is heated at 90° C. for 16 h. The solution is poured into water and extracted with EtOAc (2×200 mL). The organic layer is dried over sodium sulfate, filtered, evaporated in vacuo. The residue is chromatographed on silica gel eluting with EtOAc to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-4-fluoro-phenyl)-2-methyl-propionic acid (100 mg), which is dissolved in THF (4 mL) and treated with 4 N HCl in 1,4-dioxane (1 mL). The mixture is concentrated in vacuo and the residue is suspended in ether (25 mL). The solid is formed and filtered under nitrogen to afford 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-4-fluoro-phenyl)-2-methyl-propionic acid hydrochloride (67 mg, Example 99). MS: 478 (M+H); 1H NMR (300 MHz, NMR, CD3OD) □7.8, (d, 1H, J=0.3 Hz); 7.4 (m, 2H); 7.35 (s, 1H); 7-7.15 (m, 4H); 6.6 (s, 1H); 4.2 (s, 3H); 3.6 (m, 2H); 3.05 (t, 2H); 1.65 (s, 6H). IC50=0.5 nM

Workup

  1. extractionextracted with EtOAc (2×200 mL)
  2. dry with materialThe organic layer is dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue is chromatographed on silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-073e9733127f41839c870c0d6ed1a75d
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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