Triethylamine → 2-Isopropyl-4-methyl-6-morpholin-4-yl-N-(4,4,4-trifluoro-3-hydroxy-butyl)-pyridine-3-carboxylic acid amide

HRID 1753912Notes

Reaction equation

HRID 1753912 reaction equation
[CH:1]([C:4]1[C:9]([C:10]([OH:12])=O)=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:5]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.Cl.[NH2:28][CH2:29][CH2:30][CH:31]([OH:36])[C:32]([F:35])([F:34])[F:33]>O1CCCC1.C(OCC)(=O)C.[Cl-].[NH4+]>[CH:1]([C:4]1[C:9]([C:10]([NH:28][CH2:29][CH2:30][CH:31]([OH:36])[C:32]([F:35])([F:34])[F:33])=[O:12])=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:5]=1)([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 545928324-Amino-1,1,1-trifluorobutan-2-ol hydrochlorideHCID 708170442-Isopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid

Product 1

HCID 708168272-Isopropyl-4-methyl-6-morpholin-4-yl-N-(4,4,4-trifluoro-3-hydroxy-butyl)-pyridine-3-carboxylic acid amideYield 60%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 2-isopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid (synthesized similar to the methods described in sections a) to d) of example X1) (1.40 g, 5.30 mmol) in tetrahydrofuran (40 ml) are added triethylamine (2.9 ml, 21.2 mol) and 0-(7-azabenzotriazol-1-yl)N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.9 g, 5.3 mmol). The mixture is stirred for 15 min at RT, before 4-amino-1,1,1-trifluorobutan-2-ol hydrochloride (1.05 g, 5.8 mmol) is added and stirring is continued for 18 h. After completion of the reaction, the mixture is diluted with ethyl acetate and 10% aqueous ammonium chloride. The organic layer is separated and washed with saturated sodium hydrogencarbonate solution and brine, dried over magnesium sulphate and evaporated to dryness. The crude product is purified by flash chromatography (silica gel, 50% ethyl acetate/cyclohexane) to yield 2-Isopropyl-4-methyl-6-morpholin-4-yl-N-(4,4,4-trifluoro-3-hydroxy-butyl)-pyridine-3-carboxylic acid amide (example X6) (1.24 g, 3.18 mmol, 60%). [M+H]+390.2.

Workup

  1. additionis added
  2. customAfter completion of the reaction
  3. customThe organic layer is separated
  4. washwashed with saturated sodium hydrogencarbonate solution and brine
  5. dry with materialdried over magnesium sulphate
  6. customevaporated to dryness
  7. customThe crude product is purified by flash chromatography (silica gel, 50% ethyl acetate/cyclohexane)

Sources & evidence

ORD record
ord-3f01316169d04c97bc0891c184758b1c
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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