Cesium carbonate → HCID 86710355, compound

HRID 1398361Notes

Reaction equation

HRID 1398361 reaction equation
Br[C:2]1[C:18]([O:19][CH2:20][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH:23]2[CH2:25][CH2:24]2)=[CH:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][C:9]=3[CH3:14].[CH3:34]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+].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.O>[CH:23]1([CH2:22][C@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:20][O:19][C:18]2[C:2]([CH3:34])=[CH:3][C:4]3[C:13]4[C:8](=[C:9]([CH3:14])[N:10]=[CH:11][CH:12]=4)[C:7](=[O:15])[N:6]([CH3:16])[C:5]=3[CH:17]=2)[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 574072TrimethylboroxineHCID 86710356HCID 86710356, compound

Product 1

HCID 86710355HCID 86710355, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

An ambient temperature mixture of (S)-tert-butyl (1-((9-bromo-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-3-cyclopropylpropan-2-yl)carbamate (51 mg, 0.099 mmol), trimethylboroxine (0.015 mL, 0.109 mmol), PdCl2(dppf)-CH2Cl2 Adduct (8.06 mg, 9.88 μmol), cesium carbonate (64.4 mg, 0.198 mmol), 1,4-dioxane (1 mL), and water (0.33 mL) was charged to a pressure rated vial and purged with a stream of nitrogen for 10 minutes. The vial was sealed and stirred under nitrogen at 75° C. for 12 h. The resulting mixture was cooled to room temperature and vacuum filtered. The filtrate was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and brine. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The pooled organics were dried over magnesium sulfate, filtered, and concentrated to an oil. The oil was purified via silica gel chromatography (1% 2M ammonia in methanol/dichloromethane) to afford (S)-tert-butyl (1-cyclopropyl-3-((4,6,9-trimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (41 mg, 0.091 mmol, 92% yield) as a colorless oil. LC/MS, (ESI) m/z 452.3 [(M+H)+, calcd for C26H34N3O4 452.3]; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.59 (d, J=5.8 Hz, 1H), 7.90 (s, 1H), 7.78 (d, J=5.8 Hz, 1H), 6.74 (s, 1H), 4.91 (d, J=7.3 Hz, 1H), 4.35-4.04 (m, 3H), 3.71 (s, 3H), 3.14 (s, 3H), 2.31 (s, 3H), 1.72-1.59 (m, 2H), 1.48 (s, 9H), 0.86-0.70 (m, 1H), 0.60-0.44 (m, 2H), 0.21-0.00 (m, 2H).

Workup

  1. additionwas charged to a pressure
  2. custompurged with a stream of nitrogen for 10 minutes
  3. customThe vial was sealed
  4. temperatureThe resulting mixture was cooled to room temperature
  5. filtrationvacuum filtered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was partitioned between ethyl acetate and brine
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted twice more with ethyl acetate
  10. dry with materialThe pooled organics were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to an oil
  13. customThe oil was purified via silica gel chromatography (1% 2M ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-a06513a3e4e84618aca6171a69679f43
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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