Ammonia → HCID 11718205, compound

HRID 1921914Notes

Reaction equation

HRID 1921914 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20](Br)[N:19]=2)[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:39]2[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=2)O1.N>C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]([CH2:17][C:18]2[N:19]=[C:20]([C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)[CH:21]=[CH:22][CH:23]=2)[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 10340Sodium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 59186793HCID 59186793, compound

Product 1

HCID 11718205HCID 11718205, compound

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
86 °C

Procedure

To a solution of 4-{[(6-bromopyridin-2-ylmethyl)methylamino]methyl}piperidine-1-carboxylic acid tert-butyl ester (Preparation 4, 88 mg, 0.28 mmol) in toluene (5 mL, anhydrous) was added palladium tetrakis(triphenylphosphine) (13 mg, 0.01 mmol) and sodium carbonate (53 mg in 1.5 mL water, deoxygenated). To the vigorously stirred biphasic mixture was added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridine 57 mg, 0.28 mmol) and the reaction mixture heated to 86° C. (bath) for 3 days. The reaction mixture was allowed to cool to rt then aqueous ammonia (2M, 15 mL) was added with vigorous stirring. After 10 min, ethyl acetate (30 mL) was added and the layers separated. The aqueous was extracted with ethyl acetate (2×20 mL) and the combined organics washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. Purification via flash chromatography (5% MeOH/CH2Cl2) afforded the title compound: δH (CDCl3): 0.96-1.12 (2H, m), 1.43 (9H, s), 1.63-1.73 (1H, m), 1.78 (2H, d), 2.26-2.32 (5H, m), 2.69 (2H, t), 3.72 (2H, s), 4.00-4.14 (2H, m), 7.51 (1H, d), 7.65 (1H, d), 7.77 (1H, t), 7.88 (2H, d), 8.69 (2H, d). RT=2.38 min; m/z (ES+)=397 [M+H]+.

Workup

  1. temperatureto cool to rt
  2. customthe layers separated
  3. extractionThe aqueous was extracted with ethyl acetate (2×20 mL)
  4. washthe combined organics washed with brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification via flash chromatography (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ec993dabcf7d49f59604972a4eeac513
Source dataset
uspto-grants-2012_05
Patent number
US08173807B2

Reaction notes

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