Cesium carbonate → 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester

HRID 2110707

Reaction equation

HRID 2110707 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]([C:26]([CH3:31])([CH3:30])[C:27]([OH:29])=[O:28])[CH:23]=[CH:24][CH:25]=2)[CH:13]=1.[C:32](=[O:40])([O:37][CH2:38][CH3:39])[O:33][CH:34](Cl)[CH3:35].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O>[CH2:34]([O:33][C:32]([O:37][CH:38]([O:28][C:27](=[O:29])[C:26]([C:22]1[CH:23]=[CH:24][CH:25]=[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)([CH3:31])[CH3:30])[CH3:39])=[O:40])[CH3:35]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 162095Carbonic acid, 1-chloroethyl ethyl esterHCID 11669780Pgd2-IN-1

Product 1

HCID 576360192-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [100 mg, 0.218 mmol, Example 49(b)] in dimethylformamide (2 mL) is added 1-chloroethyl ethyl carbonate (0.053 mL, 0.392 mmol) and Cs2CO3 (142 mg, 0.436 mmol). The mixture is heated under microwave at 110° C. for 10 minutes, quenched with water, and extracted with ethyl acetate. Combined organic layers are washed with brine, dried over sodium sulfate and concentrated. The residue is subjected to silica gel chromatography eluting with 0 to 40% EtOAc in heptane to obtain 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester as an oil which is treated with 1M hydrogen chloride in ether affording 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester hydrochloride [80 mg, 64%, Example 50] as a solid. LC/MS: RT=2.94 minutes, MS: 576 (M+H). 1H NMR [300 MHz. (CD3)2SO]: □7.36-7.8 (7H, m), 6.64 (1H, q), 6.64 (1H, s), 4.05 (2H, q), 3.96 (3H, s), 3.68 (2H, m), 3 (2H, m), 1.57 (6H, s), 1.38 (3H, d), 1.15 (3H, t). IC50=4 nM

Workup

  1. customquenched with water
  2. extractionextracted with ethyl acetate
  3. washCombined organic layers are washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. washeluting with 0 to 40% EtOAc in heptane

Sources & evidence

ORD record
ord-299aa35483fc494da8e40559bfe1bffd
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Linked notes

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