4-Toluenesulfonyl chloride → [2-Methoxy-6-(5-methyl-[1,3,4]oxadiazol-2-yl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine

HRID 2110694Notes

Reaction equation

HRID 2110694 reaction equation
[C:1]([NH:4][NH:5][C:6]([C:8]1[CH:13]=[C:12]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[N:11]=[C:10]([O:25][CH3:26])[N:9]=1)=[O:7])(=O)[CH3:2].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC>C1COCC1>[CH3:26][O:25][C:10]1[N:11]=[C:12]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH:13]=[C:8]([C:6]2[O:7][C:1]([CH3:2])=[N:4][N:5]=2)[N:9]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 690709042-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidine-4-carboxylic acid N'-acetyl-hydrazide

Product 1

HCID 11501025[2-Methoxy-6-(5-methyl-[1,3,4]oxadiazol-2-yl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amineYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidine-4-carboxylic acid [100 mg, 0.33 mmol, Intermediate (56)] in dimethylformamide (1 mL) is added N,N-diisopropylethylamine (145 μL, 0.83 mmol) followed by TBTU (128 mg, 0.4 mmol). Stirred the reaction mixture for 5 minutes before adding acetic hydrazide (37 mg, 0.5 mmol) and continued stirring the reaction mixture overnight at ambient temperature. The reaction mixture is poured into water (25 mL) and subsequently extracted three times with 25 mL ethyl acetate. The combined organic extracts are washed three times with 25 mL water, with 25 mL brine, dried over magnesium sulfate, filtered and concentrated by rotary evaporator. The material obtained is subjected to flash column chromatography on silica (10 g) eluting with 0 to 5% MeOH in DCM gradient to afford 2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidine-4-carboxylic acid N′-acetyl-hydrazide (42 mg). A mixture of 2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidine-4-carboxylic acid N′-acetyl-hydrazide (42 mg, 0.12 mmol), p-toluenesulfonylchloride (34 mg, 0.18 mmol) and PS-BEMP (218 mg, 0.48 mmol) in THF (1.5 mL) is irradiated in a microwave to 140° C. for 6 minutes. The material is filtered and absorbed onto silica gel and subjected to flash column chromatography on silica gel eluting with 10 to 50% EtOAc in heptane gradient to afford [2-methoxy-6-(5-methyl-[1,3,4]oxadiazol-2-yl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine [25.1 mg, 63%, Example 44]. LCMS: RT=2.64 minutes, MS: 342 (M+H). IC50=55 nM

Workup

  1. customis irradiated in a microwave to 140° C. for 6 minutes
  2. filtrationThe material is filtered
  3. customabsorbed onto silica gel

Sources & evidence

ORD record
ord-f42d293962064cbbb87f8ed867eb0b6a
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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