Dimethylamine → HCID 11660777, compound

HRID 272947Notes

Reaction equation

HRID 272947 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].F[P-](F)(F)(F)(F)F.N1(O[C:43](N(C)C)=[N+:44](C)[CH3:45])C2C=CC=CC=2N=N1.Cl.CNC.N1C=CC=CC=1.CNC>CN(C)C=O.C(O)C.O>[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]([N:44]([CH3:45])[CH3:43])=[O:24])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 674DimethylamineHCID 1049PyridineHCID 10473Dimethylamine, hydrochlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 598374534-{4-[(1-Isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxylic acid

Product 1

HCID 11660777HCID 11660777, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-{4-[(1-Isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxylic acid (150 mg, 3.9 mmol), O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (222 mg, 5.8 mmol), dimethylamine hydrochloride (96 mg, 1.1 mmol), pyridine (126 uL, 1.56 mmol) were combined and dissolved in dimethylformamide (2 mL). The reaction mixture was stirred at ambient temperature for 18 hours. Further O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (222 mg, 5.8 mmol) and dimethylamine in ethanol (33%) (500 μL) was added and the reaction mixture was stirred at ambient temperature for 18 hours. The reaction mixture was diluted with water (20 mL) and was then extracted with ethyl acetate (2×40 mL). The combined organic extracts were dried using Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:ammonia (97:3:0.3) to dichloromethane:methanol:ammonia (90:10:1) to give a compound as a clear colourless oil. This was dissolved in ethyl acetate (70 mL) and washed with saturated NaHCO3 solution (2×10 mL). The organic extract was dried using Na2SO4, filtered and concentrated in vacuo to give the title compound as a clear crystalline solid (72 mg, 50%). 1H NMR (400 MHz, CD3OD) δ7.2 (d, 2H), 6.95 (d, 2H), 4.4 (m, 1H), 3.85 (m, 2H), 3.7 (m, 2H), 2.9-2.5 (m, 11H), 2.28 (m, 2H), 2.0 (m, 4H), 1.8 (m, 2H), 1.1 (d, 6H)

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 18 hours
  2. extractionwas then extracted with ethyl acetate (2×40 mL)
  3. customThe combined organic extracts were dried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe compound was purified by column chromatography on silica gel
  7. washeluting with dichloromethane:methanol:ammonia (97:3:0.3) to dichloromethane:methanol:ammonia (90:10:1)

Sources & evidence

ORD record
ord-ccf507a5682946aea0f8ecf7c215a18c
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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