Pyridine → HCID 11689911, compound

HRID 272948Notes

Reaction equation

HRID 272948 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23](O)=[O:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[CH2:26]([NH:28][CH2:29][CH3:30])[CH3:27].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.N1C=CC=CC=1>CN(C)C=O.O>[CH:1]([N:4]1[CH2:5][CH2:6][CH:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23]([N:28]([CH2:29][CH3:30])[CH2:26][CH3:27])=[O:24])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:13][CH:12]=2)[CH2:8][CH2:9]1)([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 1049PyridineHCID 8021Diethylamine2×HCID 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 11689911HCID 11689911, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

4-{4-[(1-Isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxylic acid (86 mg, 0.2 mol), diethylamine (27 μL, 0.26 mmol), O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (108 mg, 0.29 mmol), pyridine (53 uL, 0.66 mmol) were combined and dissolved in dimethylformamide (1.5 mL). The reaction mixture was stirred at 60° C. for 5 hours. Further diethylamine was added (500 μL). The reaction mixture was stirred at ambient temperature for 60 hours. The reaction mixture was diluted with water (25 mL), and extracted with ethyl acetate (2×35 mL). The combined organics were dried using Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography using 15 g of silica gel, eluting with dichloromethane:methanol:ammonia (96:4:0.4) to dichloromethane:methanol:ammonia (90:10:1) to give the title compound as a clear yellow oil (10 mg, 11%). 1H NMR (400 MHz, CD3OD) δ7.2 (d, 2H), 6.95 (d, 2H), 4.4 (m, 1H), 3.85-3.7 (m, 4H), 3.3 (m, 2H), 3.05-2.9 (m, 5H), 2.6 (m, 2H), 2.25 (d, 2H), 2.0 (m, 4H), 1.8 (m, 2H), 1.1 (m, 9H), 0.63 (m, 3H)

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 60 hours
  2. extractionextracted with ethyl acetate (2×35 mL)
  3. customThe combined organics were dried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe compound was purified by column chromatography
  7. washeluting with dichloromethane:methanol:ammonia (96:4:0.4) to dichloromethane:methanol:ammonia (90:10:1)

Sources & evidence

ORD record
ord-56f2ce524eec4657b4a1dc729c5769bf
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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