Pyridinium chloride → Akt1 and Akt2-IN-1

HRID 1678757Notes

Reaction equation

HRID 1678757 reaction equation
C[O:2][C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:7]([C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]3[CH2:25][CH2:24][CH:23]([C:26]4[N:30]=[C:29]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=5)[NH:28][N:27]=4)[CH2:22][CH2:21]3)=[CH:15][CH:14]=1)=[N:8]2.Cl.N1C=CC=CC=1>O.C([O-])(O)=O.[Na+]>[C:37]1([C:6]2[C:7]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][N:20]4[CH2:25][CH2:24][CH:23]([C:26]5[N:30]=[C:29]([C:31]6[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=6)[NH:28][N:27]=5)[CH2:22][CH2:21]4)=[CH:15][CH:14]=3)=[N:8][C:9]3[CH:10]=[CH:11][NH:12][C:3](=[O:2])[C:4]=3[CH:5]=2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 2

HCID 10176127Pyridinium chlorideHCID 1784940915-methoxy-3-phenyl-2-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-1,6-naphthyridine

Product 1

HCID 178518688Akt1 and Akt2-IN-1

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 5-methoxy-3-phenyl-2-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-1,6-naphthyridine (725 mg, 1.31 mmol) and pyridine hydrochloride (6.9 gm, ˜60 mmol) was heated at 150° C. for ten minutes. The cooled residue was dissolved in the minimum amount of water and neutralized with aqueous NaHCO3. The precipitated solid was collected by filtration and purified by column chromatography on silica gel eluting with 1-14% methanol/ethyl acetate (sat'd NH4OH). The isolated product was digested in methanol/acetonitrile to give pure product. 1H NMR (500 MHz, DMSO-d6): δ 11.58 (1H, d, J=4.8 Hz), 8.68 (1H, br s), 8.39 (1H, s), 8.03 (1H, d, J=7.3 Hz), 7.50 (2H, t, J=6.5 Hz), 7.31-7-33 (5H, m), 7.24-7.25 (4H, m), 6.79 (2H, d, J=7.3 Hz), 3.50 (2H, s), 2.84 (2H, br d, J=10.5 Hz), 2.72 (1H, m), 2.08 (2H, br t, J=11 Hz), 1.95 (2H, br d, J=11.6 Hz), 1.77 (2H, m). m/e (m+1): 540.3, 270.9 [(m+2)/2].

Workup

  1. filtrationThe precipitated solid was collected by filtration
  2. custompurified by column chromatography on silica gel eluting with 1-14% methanol/ethyl acetate (sat'd NH4OH)
  3. customto give pure product

Sources & evidence

ORD record
ord-df3fbb32857f4126a52752670814c492
Source dataset
uspto-grants-2011_08
Patent number
US08008317B2

Reaction notes

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