2-Amino-2-methyl-1-propanol → 6-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-pyridazine-3-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide

HRID 548901Notes

Reaction equation

HRID 548901 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[N:20]=[N:19][C:18]([C:21]([OH:23])=O)=[CH:17][CH:16]=3)=[C:11]([CH3:24])[O:10][N:9]=2)=[N:6][CH:7]=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.[NH2:56][C:57]([CH3:61])([CH3:60])[CH2:58][OH:59]>CN(C=O)C.O>[OH:59][CH2:58][C:57]([NH:56][C:21]([C:18]1[N:19]=[N:20][C:15]([O:14][CH2:13][C:12]2[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=3)=[N:9][O:10][C:11]=2[CH3:24])=[CH:16][CH:17]=1)=[O:23])([CH3:61])[CH3:60]

Participants

7

Reactant 4

HCID 118072-Amino-2-methyl-1-propanolHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 671576016-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-pyridazine-3-carboxylic acid

Product 1

HCID 426306296-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-pyridazine-3-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amideYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-[3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-pyridazine-3-carboxylic acid (69.4 mg, 0.21 mmol) in DMF (1.1 mL) were added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (74.1 mg, 0.23 mmol), N,N-diisopropyl ethyl amine (179 μL, 1.05 mmol) and 2-amino-2-methyl-1-propanol (20.6 mg, 0.23 mmol). The resulting reaction mixture was stirred for 30 min at room temperature and diluted with water. The mixture was then extracted with ethyl acetate and the combined organic layers washed with aqueous sodium carbonate (saturated) and dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=1:0 to 3:7) afforded the title compound (74 mg, 88%) which was obtained as an off white solid. MS: m/e=402.4 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. extractionThe mixture was then extracted with ethyl acetate
  3. washthe combined organic layers washed with aqueous sodium carbonate (saturated)
  4. dry with materialdried over sodium sulfate
  5. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate=1:0 to 3:7)

Sources & evidence

ORD record
ord-30d9c987e0c34e5eb2f213f03af6c1cd
Source dataset
uspto-grants-2011_05
Patent number
US07943619B2

Reaction notes

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