Sodium Carbonate → HCID 58094316, compound

HRID 1034945Notes

Reaction equation

HRID 1034945 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH2:24][CH2:23][O:22][C@H:21]([CH3:25])[CH2:20]4)=[C:15]([CH3:26])[CH:14]=3)[N:11]=1)[C:8](=[O:27])[NH:7][CH:6]=[CH:5]2.[CH3:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>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.C(Cl)Cl.CO.O>[CH3:26][C:15]1[CH:14]=[C:13]([NH:12][C:10]2[N:11]=[C:2]([C:32]3[CH:31]=[N:30][C:29]([CH3:28])=[CH:34][CH:33]=3)[CH:3]=[C:4]3[C:9]=2[C:8](=[O:27])[NH:7][CH:6]=[CH:5]3)[CH:18]=[CH:17][C:16]=1[N:19]1[CH2:24][CH2:23][O:22][C@H:21]([CH3:25])[CH2:20]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 164142722-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 58093979HCID 58093979, compound

Product 1

HCID 58094316HCID 58094316, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-6-chloro-8-(3-methyl-4-(2-methylmorpholino)phenylamino)-2,7-naphthyridin-1(2H)-one (770 mg, 2.0 mmol), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.8 g, 3.65 mmol), Pd(PPh3)4 (200.0 mg, 0.173 mmol) and Na2CO3 (1.0 g, 9.45 mmol) in a mixed solvent of dioxane (16.0 mL) and H2O (4.0 mL) was purged with N2, heated at 90° C. for 16 hours, evaporated to result in a residue which was subjected to chromatography with gradient mixed solvents from DCM/MeOH/28% aqueous NH4OH (49:10:1) to (19:10:1) afforded a product which was then recrystallized in toluene to afford the title compound. 1H NMR (DMSO-d6) δ 1.12 (d, J=6.4 Hz, 3H, CH3), 2.31 (s, 3H, CH3), 2.42 (m, 1H), 2.55 (s, 3H, CH3), 2.70 (m, 1H), 2.85-2.95 (2H), 3.65-3.73 (2H), 3.85 (m, 1H), 6.53 (d, J=7.2 Hz, 1H), 7.07 (d, J=8.4 Hz, 1H), 7.42 (d, J=8.4 Hz, 1H), 7.43 (d, J=7.2 Hz, 1H), 7.48 (s, 1H), 7.66 (d, J=2.4 Hz, 1H), 7.74 (dd, J=8.0, 2.4 Hz, 1H), 8.35 (dd, J=8.8, 2.4 Hz, 1H), 9.20 (s, 1H), 11.77 (br s, 1H, NH), 11.92 (br s, 1H, NH); ESI-MS ink 442.2 (MH+); Anal. Calcd for C26H27N5O2: C, 70.73; H, 6.16; N, 15.86. Found: C, 70.73; H, 6.13; N, 15.83.

Workup

  1. customwas purged with N2
  2. customevaporated
  3. customto result in a residue which
  4. customafforded a product which
  5. customwas then recrystallized in toluene

Sources & evidence

ORD record
ord-ed2614b11e5c498cb832afd3ae065030
Source dataset
uspto-grants-2013_10
Patent number
US08546370B2

Reaction notes

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