Sodium Carbonate → HCID 118092764, compound

HRID 2207356Notes

Reaction equation

HRID 2207356 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:15]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:13]=[C:12]([CH3:25])[CH:11]=2)[N:4]=1.Br[C:27]1[N:32]=[C:31]([CH2:33][CH2:34][C:35]([O:37][CH2:38]C)=[O:36])[CH:30]=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:15]=[C:14]([C:27]3[N:32]=[C:31]([CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])[CH:30]=[CH:29][CH:28]=3)[CH:13]=[C:12]([CH3:25])[CH:11]=2)[N:4]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58456328HCID 58456328, compoundHCID 87253288HCID 87253288, compound

Product 1

HCID 118092764HCID 118092764, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-methoxy-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine (0.045 g, 0.13 mmol), ethyl 3-(6-bromopyridin-2-yl)propanoate (0.037 g, 0.15 mmol), PdCl2(dppf)-CH2Cl2 (0.016 g, 0.020 mmol), and Na2CO3 (2.0 M in water, 0.13 mL, 0.26 mmol) in dioxane (0.75 mL) was purged with argon and heated to 110° C. for 12 hours. Upon cooling, NaOH (1.0 M in water, 0.50 mL) and MeOH (0.50 mL) were added to the reaction mixture and irradiated in a microwave reactor for 10 minutes at 110° C. Silica Supported-DMT (0.088 g, 0.13 mmol, 0.57 mmol/g) was added to the reaction mixture and shaken for 5 hours at ambient temperature. The reaction was passed through a syringe filter and the eluent was evaporated under reduced pressure. The residue was suspended in DMSO (1.5 mL) and was purified by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v formic acid modifier) to afford methyl 3-(6-(3-((4-methoxypyrimidin-2-yl)amino)-5-methylphenyl)pyridin-2-yl)propanoate. LRMS (ESI) calc'd for C20H21N4O3 [M+H]+: 365. Found: 365. 1H NMR (600 MHz, DMSO-d6) δ 9.54 (s, 1H), 8.33 (s, 1H), 8.18 (d, J=5.6, 1H), 7.73 (t, J=7.7, 1H), 7.64 (d, J=7.8, 1H), 7.61 (s, 1H), 7.44 (s, 1H), 7.19 (d, J=7.6, 1H), 6.25 (d, J=5.6, 1H), 3.93 (s, 3H), 2.99 (t, J=7.4, 2H), 2.71 (t, J=7.4, 2H), 2.33 (s, 3H).

Workup

  1. customwas purged with argon
  2. temperatureUpon cooling
  3. additionNaOH (1.0 M in water, 0.50 mL) and MeOH (0.50 mL) were added to the reaction mixture
  4. customirradiated in a microwave reactor for 10 minutes at 110° C
  5. additionSilica Supported-DMT (0.088 g, 0.13 mmol, 0.57 mmol/g) was added to the reaction mixture
  6. customThe reaction was passed through a syringe
  7. filtrationfilter
  8. customthe eluent was evaporated under reduced pressure
  9. customwas purified by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v formic acid modifier)

Sources & evidence

ORD record
ord-7a24ad3649d94c7cbf97a80f5de2cd46
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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