Sodium Carbonate → HCID 59599417, compound

HRID 1627564Notes

Reaction equation

HRID 1627564 reaction equation
[OH:1][C:2]1([CH2:15][N:16]2[CH:20]=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:18]=[N:17]2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Cl:30][C:31]1[C:36]([F:37])=[CH:35][CH:34]=[C:33]([Cl:38])[C:32]=1[CH:39]([O:41][C:42]1[C:43]([NH2:49])=[N:44][CH:45]=[C:46](I)[CH:47]=1)[CH3:40].C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[NH2:49][C:43]1[N:44]=[CH:45][C:46]([C:19]2[CH:18]=[N:17][N:16]([CH2:15][C:2]3([OH:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:9])[CH2:4][CH2:3]3)[CH:20]=2)=[CH:47][C:42]=1[O:41][CH:39]([C:32]1[C:33]([Cl:38])=[CH:34][CH:35]=[C:36]([F:37])[C:31]=1[Cl:30])[CH3:40]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 211113953-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-iodopyridin-2-amineHCID 54579457HCID 54579457, compound

Product 1

HCID 59599417HCID 59599417, compoundYield 28.5%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
85 °C

Procedure

A reaction mixture of compound (3-4) (361 mg; 0.89 mmol) and 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-iodopyridin-2-amine (3-5) (378 mg; 0.89 mmol) in 9.0 mL of ethylene glycol dimethylether, anhydrous (DME) was purged with N2 for 15 minutes, then Pd(II)(PPh3)2Cl2 (32 mg, 0.05 mmol) was added and continued to purge with N2 for another 15 minutes. Another 1.0 N Na2CO3 solution (3.9 mL; 3.9 mmol) was added after purging with N2 for 15 minutes. The resulting mixture was stirred at 85° C. under N2 for overnight. The reaction mixture was filtered through Celite pad and washed well with MeOH. The filtrate was concentrated by vacuum. The residue was partitioned between EtOAc (200 mL) and saturated NaHCO3 solution (2×50 mL); brine (50 mL). The organic layer was dried (Na2SO4), then concentrated by vacuum. The residue was purified by Dionex system (25% to 95% MeCN:H2O w 0.1% HOAc buffer) to collect the desired fraction to afford 147 mg of (3-6) as a white solid (28% yield). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.34-1.39 (m, 9H) 1.70-1.77 (m, 2H) 1.79 (d, J=6.57 Hz, 3H) 3.06 (d, J=12.63 Hz, 2H) 3.62 (s, 2H) 4.03 (s, 2H) 4.79 (s, 1H) 5.66 (s, 2H) 6.08 (d, J=6.82 Hz, 1H) 6.86 (d, J=1.52 Hz, 1H) 7.44 (t, J=8.72 Hz, 1H) 7.51-7.58 (m, 2H) 7.58-7.65 (m, 2H) 7.73 (d, J=1.52 Hz, 1H) 7.78 (s, 1H). LCMS calcd for C27H32Cl2FN5O4 (M+H) 581, found 581. HPLC purity 87%.

Workup

  1. customwas purged with N2 for 15 minutes
  2. customto purge with N2 for another 15 minutes
  3. customafter purging with N2 for 15 minutes
  4. filtrationThe reaction mixture was filtered through Celite pad
  5. washwashed well with MeOH
  6. concentrationThe filtrate was concentrated by vacuum
  7. customThe residue was partitioned between EtOAc (200 mL) and saturated NaHCO3 solution (2×50 mL)
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. concentrationconcentrated by vacuum
  10. customThe residue was purified by Dionex system (25% to 95% MeCN:H2O w 0.1% HOAc buffer)
  11. customto collect the desired fraction

Sources & evidence

ORD record
ord-b881927a8d064644aabbd48acdc74285
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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