Cesium carbonate → (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-oxo-2,6-naphthyridin-2(1H)-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetate

HRID 879364Notes

Reaction equation

HRID 879364 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:27]([CH3:28])=[CH:26][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21](Cl)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[C:36]1(=[O:46])[C:45]2[C:40](=[CH:41][N:42]=[CH:43][CH:44]=2)[CH:39]=[CH:38][NH:37]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C@@H:6]([C:12]1[C:27]([CH3:28])=[CH:26][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([N:37]4[CH:38]=[CH:39][C:40]5[C:45](=[CH:44][CH:43]=[N:42][CH:41]=5)[C:36]4=[O:46])[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:29]1[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 8177432,6-Naphthyridin-1-olHCID 86700142(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700170(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-oxo-2,6-naphthyridin-2(1H)-yl)pyridin-4-yl)benzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (26.0 mg, 0.049 mmol) in anhydrous THF (0.6 mL) was added 2,6-naphthyridin-1(2H)-one (11.0 mg, 0.074 mmol), Xantphos (4.0 mg, 0.006 mmol), Cs2CO3 (27.0 mg, 0.084 mmol) and Pd2(dba)3 (2.0 mg, 0.002 mmol). The reaction was degassed for 5 minutes with N2 and then heated at 100° C. overnight. After cooling, the reaction mixture was diluted with EtOAc, extracted with H2O, brine, dried over Na2SO4, filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 90% ethyl acetate/hexanes) to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C35H32ClN4O4S: 639.2; found: 639.3.

Workup

  1. customThe reaction was degassed for 5 minutes with N2
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with EtOAc
  4. extractionextracted with H2O, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (silica gel, 0 to 90% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4bd13d7095f44dd0907dc012e2021d6e
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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