Water → (3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoylamino)-acetic acid ethyl ester

HRID 216189Notes

Reaction equation

HRID 216189 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([O:18][CH3:19])[N:15]=[C:14]([C:20]2[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=2)[C:23](O)=[O:24])[CH:13]=1.C(N(C(C)C)CC)(C)C.Cl.[CH2:39]([O:41][C:42](=[O:45])[CH2:43][NH2:44])[CH3:40].O>CN(C)C=O>[CH2:39]([O:41][C:42](=[O:45])[CH2:43][NH:44][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][CH:28]=[C:20]([C:14]2[CH:13]=[C:12]([NH:11][CH2:10][CH2:9][C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[N:17]=[C:16]([O:18][CH3:19])[N:15]=2)[CH:21]=1)[CH3:40]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2723640Glycine ethyl ester, hydrochlorideHCID 533205273-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid

Product 1

HCID 11706060(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoylamino)-acetic acid ethyl esterYield 79.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid [127 mg, 0.3 mmol, Example 35(w)], O-(benzotriazol-1-yl)-N,N,N′N′-tetramethyluronium tetrafluoroborate (116 mg, 0.36 mmol), diisopropylethylamine (131 μL, 0.75 mmol) and glycine ethyl ester hydrochloride (63 mg, 0.45 mmol) in dimethylformamide (3 mL) is stirred at ambient temperature for 18 hours. The mixture is poured into water and extracted three times with EtOAc (20 mL). The organic extracts are combined and washed twice with water (20 mL), dried over magnesium sulfate, filtered and concentrated by rotary evaporator to provide a solid. The solid is absorbed onto silica and subjected to flash column chromatography on silica (40 g) eluting with 0% to 50% ethyl acetate/heptane gradient, to afford (3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoylamino)-acetic acid ethyl ester [120 mg, 79%, Example 58]. MS: 503 (M+H).

Workup

  1. extractionextracted three times with EtOAc (20 mL)
  2. washwashed twice with water (20 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporator
  6. customto provide a solid
  7. customThe solid is absorbed onto silica
  8. washeluting with 0% to 50% ethyl acetate/heptane gradient

Sources & evidence

ORD record
ord-970956d6a5ab467496663ebbfb1fdff8
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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