Sodium Carbonate → (6-(2,6-Diethyl-phenyl)-2-methyl-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-4-yl)-pyrrolidin-1-yl-methanone

HRID 1392672Notes

Reaction equation

HRID 1392672 reaction equation
Cl[C:2]1[C:7]([CH2:8][N:9]([CH3:20])[CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12][CH2:11]2)=[C:6]([C:21]([N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[O:22])[CH:5]=[C:4](Cl)[N:3]=1.[CH2:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][CH3:38])[C:32]=1B(O)O)[CH3:30].[C:42]([O-])([O-])=O.[Na+].[Na+].CB(O)O.[OH-].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCCCCC>[CH2:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][CH3:38])[C:32]=1[C:4]1[N:3]=[C:2]([CH3:42])[C:7]([CH2:8][N:9]([CH3:20])[CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12][CH2:11]2)=[C:6]([C:21]([N:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)=[O:22])[CH:5]=1)[CH3:30]

Participants

9

Reactant 5

HCID 10340Sodium Carbonate2×HCID 14798Sodium HydroxideHCID 139377Methylboronic AcidHCID 18437832(2,6-Diethylphenyl)boronic acidHCID 72355817(2,6-Dichloro-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-4-yl)-pyrrolidin-1-yl-methanone

Product 1

HCID 66993792(6-(2,6-Diethyl-phenyl)-2-methyl-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-4-yl)-pyrrolidin-1-yl-methanone

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 1140TolueneSolvent2×HCID 8058HexaneSolvent

Procedure

A mixture of (2,6-dichloro-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-4-yl)-pyrrolidin-1-yl-methanone (200 mg, 0.48 mmol), 2,6-diethyl-phenyl boronic acid (85 mg, 0.48 mmol), Na2CO3 (2 M aqueous solution, 0.48 mL, 0.96 mmol), and Pd(PPh3)4 (50 mg) is refluxed in toluene (10 mL) for 18 hours and cooled to room temperature. Methylboronic acid (286 mg, 4.78 mmol), Na2CO3 (2 M aqueous solution, 0.48 mL, 0.96 mmol), and Pd(PPh3)4 (50 mg) are added to the mixture. The resulting mixture is refluxed in toluene for another 18 hours and then cooled to room temperature. Hexane (20 mL) and 1 N NaOH (2 mL) are added. The organic layer is separated, washed with brine, dried over sodium sulfate, and solvent removed. The crude product is purified by flash column (4:1 hexane:EtOAc) to give (6-(2,6-diethyl-phenyl)-2-methyl-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-4-yl)-pyrrolidin-1-yl-methanone. 1H NMR (CDCl3) 7.51 (m, 1H), 7.28 (m, 1H), 7.14-6.98 (m, 6H), 4.02-3.80 (m, 3H), 3.65 (m, 2H), 3.25 (m, 2H), 2.75-2.34 (m, 5H), 2.10 (m, 4H), 2.05-1.85 (m, 9H), 1.76 (m, 2H), 1.03 (t, 6H).

Workup

  1. temperaturecooled to room temperature
  2. customThe organic layer is separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate, and solvent
  5. customremoved
  6. customThe crude product is purified by flash column (4:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-21f7932b984344a491a55dcd258940e3
Source dataset
uspto-grants-2008_03
Patent number
US07342115B2

Reaction notes

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