Potassium Carbonate → HCID 11690028, compound

HRID 216111Notes

Reaction equation

HRID 216111 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]2[S:13][C:12]([CH:14]=[O:15])=[CH:11][CH:10]=2)[CH:6]=[C:5]([NH:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:4]=1.S([CH2:37][N+:38]#[C-:39])(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+]>CO>[CH3:1][O:2][C:3]1[N:4]=[C:5]([NH:16][CH2:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)[CH:6]=[C:7]([C:9]2[S:13][C:12]([C:14]3[O:15][CH:39]=[N:38][CH:37]=3)=[CH:11][CH:10]=2)[N:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanideHCID 11501553HCID 11501553, compound

Product 1

HCID 11690028HCID 11690028, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirred mixture of 5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-thiophene-2-carbaldehyde [300 mg, 0.81 mmol, Example 8(b)], tosylmethylisocyanide (174 mg, 0.89 mmol), K2CO3 (246 mg 1.78 mmol) and MeOH (30 mL) is heated at reflux for 4 hours. The mixture is allowed to cool to ambient temperature, concentrated by rotary evaporator to remove the solvent. The residue is partitioned between EtOAc and water. The organic phase is dried over magnesium sulfate, filtered and concentrated. The residual solid is subjected to flash column chromatography on silica gel eluting with EtOAc and cyclohexane to afford [2-methoxy-6-(5-oxazol-5-yl-thiophen-2-yl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine [240 mg, 73%, Example 11(a)]. LCMS: RT=8.99 minutes, MS: 409 (M+H). IC50=2.3 nM

Workup

  1. temperatureis heated
  2. temperatureat reflux for 4 hours
  3. concentrationconcentrated by rotary evaporator
  4. customto remove the solvent
  5. customThe residue is partitioned between EtOAc and water
  6. dry with materialThe organic phase is dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c2414bda50a642049d449d7fb367b154
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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