Triethylamine → HCID 59837478, compound

HRID 272964Notes

Reaction equation

HRID 272964 reaction equation
CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]([N:28]1[CH2:33][CH2:32][CH:31]([O:34][C:35]2[CH:40]=[CH:39][C:38]([C:41]3([C:47]([OH:49])=O)[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[CH:37][CH:36]=2)[CH2:30][CH2:29]1)([CH3:27])[CH3:26].[CH2:50]([N:52](CC)[CH2:53]C)[CH3:51].C(NC)C>CN(C)C=O>[CH2:50]([N:52]([CH3:53])[C:47]([C:41]1([C:38]2[CH:39]=[CH:40][C:35]([O:34][CH:31]3[CH2:32][CH2:33][N:28]([CH:25]([CH3:26])[CH3:27])[CH2:29][CH2:30]3)=[CH:36][CH:37]=2)[CH2:42][CH2:43][O:44][CH2:45][CH2:46]1)=[O:49])[CH3:51]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12219N-MethylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 598374534-{4-[(1-Isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxylic acid

Product 1

HCID 59837478HCID 59837478, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(1H-Benzotriazol-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (286 mg, 0.75 mmol) was added to a solution of 4-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxylic acid (200 mg, 0.58 mmol) in N,N-dimethylformamide (6 mL). Then triethylamine (243 μL, 1.74 mmol) was added. The mixture was stirred at room temperature for 15 minutes. Ethylmethylamine (500 μL, 5.8 mmol) was added and the reaction mixture stirred at room temperature for 18 hours. The reaction was concentrated in vacuo. The residue was partitioned between aqueous sodium bicarbonate solution (30 mL) and ethyl acetate (2×75 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.5, by volume) to provide the title compound (80 mg, 35%). 1H NMR (400 MHz, CD3OD) δ 1.06-1.25 (m, 9H), 1.90-2.02 (m, 4H), 2.08-2.12 (m, 2H), 2.25-2.28 (m, 2H), 2.58 (m, 2H), 2.87 (m, 3H), 2.95 (m, 2H), 3.09-3.12 (m, 3H), 3.71-3.76 (m, 2H), 3.82-3.86 (m, 2H), 4.53 (m, 1H), 6.98 (d, 2H), 7.20 (d, 2H).

Workup

  1. stirringthe reaction mixture stirred at room temperature for 18 hours
  2. concentrationThe reaction was concentrated in vacuo
  3. customThe residue was partitioned between aqueous sodium bicarbonate solution (30 mL) and ethyl acetate (2×75 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.5, by volume)

Sources & evidence

ORD record
ord-5172bda429c84ec0868dc752792a5b5d
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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