Triethylamine → 3-Methoxy-N-(2-methyl-thiazol-4-ylmethoxy)-2-[(pyridin-4-ylmethyl)-amino]-benzamide

HRID 1663155Notes

Reaction equation

HRID 1663155 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=O.C(N(CC)CC)C.C[N+](C)=C(N(C)C)ON1C2C=CC=CC=2N=N1.F[B-](F)(F)F.Cl.[CH3:50][C:51]1[S:52][CH:53]=[C:54]([CH2:56][O:57][NH2:58])[N:55]=1>CN(C=O)C.O>[CH3:1][O:2][C:3]1[C:4]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([NH:58][O:57][CH2:56][C:54]1[N:55]=[C:51]([CH3:50])[S:52][CH:53]=1)=[O:8]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 54606663HCID 54606663, compoundHCID 589898483-Methoxy-2-[(pyridin-4-ylmethyl)-amino]-benzoic acid

Product 1

HCID 112228443-Methoxy-N-(2-methyl-thiazol-4-ylmethoxy)-2-[(pyridin-4-ylmethyl)-amino]-benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

3-Methoxy-2-[(pyridin-4-ylmethyl)-amino]-benzoic acid (200 mg, see preparation 1D) was dissolved in DMF (20 ml) and triethylamine (0.65 ml) at 50-60° C. N,N,N′,N′-Tetramethyl-O-(benzotriazole-1-yl)uronium-tetrafluoroborate (250 mg) was added and after 5 minutes O-(2-methyl-thiazol-4-ylmethyl)-hydroxylamine hydrochloride (209 mg, see preparation 12) was added. The reaction mixture was heated to 90° C. and stirred at this temperature for 2 hours. The mixture was cooled to room temperature and water was added. The mixture was extracted several times with EtOAc and the combined organic layers were washed with water, saturated aqueous sodium bicarbonate, water, and brine. The organic layer was dried (MgSO4) and evaporated under reduced pressure. The remaining material was purified by column chromatography on silica gel (elution with 1 to 4% methanol in EtOAc) and gave the title compound as an yellow oil. 13C-NMR (DMSO-d6) δ 165.3, 150.4, 150.0, 149.8, 149.3, 137.8, 122.2, 120.5, 118.8, 117.9, 114.0, 71.8, 55.7, 48.3, 18.6.

Workup

  1. customat 50-60° C
  2. additionwas added
  3. temperatureThe mixture was cooled to room temperature
  4. extractionThe mixture was extracted several times with EtOAc
  5. washthe combined organic layers were washed with water, saturated aqueous sodium bicarbonate, water, and brine
  6. dry with materialThe organic layer was dried (MgSO4)
  7. customevaporated under reduced pressure
  8. customThe remaining material was purified by column chromatography on silica gel (elution with 1 to 4% methanol in EtOAc)

Sources & evidence

ORD record
ord-4a54bf290030467893716d7e6663d365
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

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