Diisopropylethylamine → 6-((3-Butyl-5-methyl-isoxazol-4-yl)methoxy)-n-((s)-2,2,2-trifluoro-1-methyl-ethyl)-nicotinamide

HRID 1807505Notes

Reaction equation

HRID 1807505 reaction equation
[CH2:1]([C:5]1[C:9]([CH2:10][O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][N:13]=2)=[C:8]([CH3:21])[O:7][N:6]=1)[CH2:2][CH2:3][CH3:4].[CH3:22][CH:23]([NH2:28])[C:24]([F:27])([F:26])[F:25].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>CN(C=O)C>[CH2:1]([C:5]1[C:9]([CH2:10][O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([NH:28][C@@H:23]([CH3:22])[C:24]([F:27])([F:26])[F:25])=[O:18])=[CH:14][N:13]=2)=[C:8]([CH3:21])[O:7][N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 37831651,1,1-Trifluoro-2-propanamineHCID 665983356-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-nicotinic acid

Product 1

HCID 498007346-((3-Butyl-5-methyl-isoxazol-4-yl)methoxy)-n-((s)-2,2,2-trifluoro-1-methyl-ethyl)-nicotinamideYield 67.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-(3-butyl-5-methyl-isoxazol-4-ylmethoxy)-nicotinic acid (100 mg, 0.34 mmol) in DMF (2 mL) at room temperature under argon was added L-2,2,2-trifluoro-1-(methyl)ethylamine (ABCR F07820EFA, 42.9 mg, 0.38 mmol), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (121.7 mg, 0.38 mmol) and N,N-diisopropylethylamine (222.6 mg, 1.72 mmol). After 2.5 h the reaction mixture was concentrated, diluted with water and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. Purification by chromatography (silica, heptane:ethyl acetate=1:0 to 2:1) afforded the title compound (89 mg, 67%) as a light yellow oil. MS: m/e=384.3 [M−H]−.

Workup

  1. concentrationAfter 2.5 h the reaction mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by chromatography (silica, heptane:ethyl acetate=1:0 to 2:1)

Sources & evidence

ORD record
ord-25868ea89d59417e9d9d81bc752c89a4
Source dataset
uspto-grants-2013_01
Patent number
US08357703B2

Reaction notes

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