Cesium carbonate → HCID 56953334, compound

HRID 1183149Notes

Reaction equation

HRID 1183149 reaction equation
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][C:8](B3OC(C)(C)C(C)(C)O3)=[C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]3=2)[C:5](=[O:25])[N:4]([C@@H:26]2[C@@H:31]([OH:32])[CH2:30][O:29][CH2:28][CH2:27]2)[CH2:3]1.Cl.Cl[CH2:35][C:36]1[CH:41]=[CH:40][N:39]=[C:38]([CH:42]([F:44])[F:43])[CH:37]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O.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>[F:43][CH:42]([F:44])[C:38]1[CH:37]=[C:36]([CH2:35][C:8]2[CH:7]=[C:6]3[C:11](=[C:10]4[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=24)[N:2]([CH3:1])[CH2:3][N:4]([C@@H:26]2[C@@H:31]([OH:32])[CH2:30][O:29][CH2:28][CH2:27]2)[C:5]3=[O:25])[CH:41]=[CH:40][N:39]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 669790361371535-98-6HCID 67130126HCID 67130126, compound

Product 1

HCID 56953334HCID 56953334, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 1,5-anhydro-2,3-dideoxy-3-[1-methyl-4-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydrobenzo[h]quinazolin-3(2H)-yl]-L-threo-pentitol (47 mg, 0.11 mmol), 4-(chloromethyl)-2-(difluoromethyl)pyridine hydrochloride (23 mg, 0.11 mmol), cesium carbonate (98 mg, 0.30 mmol), and PdCl2(dppf)-CH2Cl2 adduct (12 mg, 0.017 mmol) in THF (0.85 mL) and water (0.10 mL) was purged subsurface with nitrogen, then capped and heated at 100° C. overnight. The reaction was diluted with water and saturated, aqueous NaHCO3, then extracted 2× with EtOAc. The organics were washed with brine, dried over MgSO4, filtered, concentrated, and dried. The residue was purified via silica gel chromatography, eluting with 20-100% ethyl acetate in hexanes to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 454.0 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=4.8 Hz, 1H), 8.28-8.31 (m, 1H), 7.92 (s, 1H), 7.76 (dd, J=7.6, 1.6 Hz, 1H), 7.52-7.61 (m, 2H), 7.47 (s, 1H), 7.12 (d, J=4.8 Hz, 1H), 6.58 (t, J=55.2 Hz, 1H), 4.70 (dd, J=32.8, 12.4 Hz, 2H), 4.62-4.69 (m, 1H), 4.40 (s, 2H), 4.17 (dd, J=10.8, 5.2 Hz, 1H), 4.06 (dd, J=7.6, 4.4 Hz, 1H), 3.73-3.82 (m, 1H), 3.51-3.58 (m, 1H), 3.25-3.30 (m, 1H), 3.02 (s, 3H), 2.62 (d, J=7.2 Hz, 1H), 1.86-2.04 (m, 2H).

Workup

  1. customcapped
  2. extractionsaturated, aqueous NaHCO3, then extracted 2× with EtOAc
  3. washThe organics were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customdried
  8. customThe residue was purified via silica gel chromatography
  9. washeluting with 20-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e4b85d4f04774250aebcda641bf830d4
Source dataset
uspto-grants-2014_03
Patent number
US08664234B2

Reaction notes

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