Sodium Carbonate → HCID 59375618, compound

HRID 2192987Notes

Reaction equation

HRID 2192987 reaction equation
[CH:1]1([C:4]#[C:5][C:6]2[C:15]3[N:14]=[C:13]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[C:12]4[CH:23]=[CH:24][C:25](Br)=[CH:26][C:11]=4[C:10]=3[C:9](=[O:28])[NH:8][CH:7]=2)[CH2:3][CH2:2]1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[N:39][NH:40][CH:41]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>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.CN(C=O)C>[CH:1]1([C:4]#[C:5][C:6]2[C:15]3[N:14]=[C:13]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[C:12]4[CH:23]=[CH:24][C:25]([C:37]5[CH:38]=[N:39][NH:40][CH:41]=5)=[CH:26][C:11]=4[C:10]=3[C:9](=[O:28])[NH:8][CH:7]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59375684HCID 59375684, compound

Product 1

HCID 59375618HCID 59375618, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

4-(cyclopropylethynyl)-9-bromo-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one (750 mg, 1.711 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (664 mg, 3.42 mmol), and PdCl2(dppf)-CH2Cl2 adduct (279 mg, 0.342 mmol) were added to a vial, followed by DMF (1.71E+04 μl) and aqueous sodium carbonate (2M) (1711 μl, 3.42 mmol). The reaction was purged with argon (subsurface bubbling) for 10 min. The reaction mixture was heated in a microwave oven at 130° C. for 45 min. The mixture was then cooled to room temperature and diluted with DMSO (˜17 mL) and filtered through a syringe filter (filter was rinsed with DMSO). This solution was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA. The fractions were combined, neutralized with NaHCO3 (sat) and extracted with dichloromethane (2×300 mL). The combined organics were washed with water (200 mL), brine (200 mL) dried over anhydrous sodium sulfate, swirled for 10 min with 1 g MP-TMT Pd scavenger resin, filtered and dried under reduced pressure to give the title compound as a yellow solid. 1H NMR (500 MHz, CD3OD) δ 13.10 (s, 1H), 11.28 (d, 1H, J=6.5 Hz), 10.02 (d, 1H, J=1.5 Hz), 8.49 (d, 1H, J=9.0 Hz), 8.28 (s, 1H), 7.96 (s, 1H), 7.83 (dd, 1H, J=8.5, 1.5 Hz), 7.49 (d, 1H, J=6.5 Hz), 7.45 (d, 1H, J=9.0 Hz), 4.87 (m, 1H), 1.53 (m, 1H) 1.21 (d, 3H, J=7 Hz), 0.98 (s, 9H), 0.88 (m, 2H), 0.72 (m, 2H). LRMS (ESI) calc'd for (C26H28N5O) [M+H]+, 426.2; found 426.2.

Workup

  1. customThe reaction was purged with argon (subsurface bubbling) for 10 min
  2. temperatureThe mixture was then cooled to room temperature
  3. additiondiluted with DMSO (˜17 mL)
  4. filtrationfiltered through a syringe
  5. filtrationfilter
  6. filtration(filter was rinsed with DMSO)
  7. customThis solution was purified by preparative HPLC Reverse phase (C-18)
  8. washeluting with Acetonitrile/Water+0.05% TFA
  9. extractionextracted with dichloromethane (2×300 mL)
  10. washThe combined organics were washed with water (200 mL), brine (200 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-6dd3e43f008a431fbc7b651821f679d2
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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