Ethanolamine → N-(2-Hydroxy-ethyl)-6-[(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-nicotinamide

HRID 1521149Notes

Reaction equation

HRID 1521149 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][NH:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH2:55]([CH2:57][NH2:58])[OH:56]>C(OCC)(=O)C.CN(C=O)C>[OH:56][CH2:55][CH2:57][NH:58][C:19](=[O:21])[C:18]1[CH:22]=[CH:23][C:15]([NH:14][CH2:13][C:3]2[C:4]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)=[N:5][O:6][C:2]=2[CH3:1])=[N:16][CH:17]=1

Participants

7

Reactant 4

HCID 700EthanolamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 684464016-[(5-Methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-nicotinic acid

Product 1

HCID 68935584N-(2-Hydroxy-ethyl)-6-[(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-nicotinamideYield 88%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 6-[(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-nicotinic acid (200 mg, 0.65 mmol) and 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (228 mg, 0.71 mmol) was added DMF (2 mL). After stirring for 2 min at ambient temperature N,N-diisopropyl ethyl amine (553 μL, 3.23 mmol) and ethanolamine (47 μl, 0.78 mmol) were added and the resulting solution was stirred for 2 h at this temperature. It was diluted with ethyl acetate (15 mL) and washed with water (20 mL) and brine (15 mL). The aqueous layers were extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate:methanol=30:70:0 to 0:95:5) afforded the title compound (200 mg, 88%) as a white solid. MS: m/e=353.2 [M+H]+.

Workup

  1. additionwere added
  2. washwashed with water (20 mL) and brine (15 mL)
  3. extractionThe aqueous layers were extracted with ethyl acetate
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate:methanol=30:70:0 to 0:95:5)

Sources & evidence

ORD record
ord-4b6a98e5dfed4f748a7de8441720655e
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

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