Cesium fluoride → (2S)-ethyl 2-(2-(azetidin-1-yl)-7-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

HRID 510248Notes

Reaction equation

HRID 510248 reaction equation
[N:1]1([C:5]2[S:6][C:7]3[C:13](OS(C(F)(F)F)(=O)=O)=[C:12]([C@H:22]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:11]([CH3:33])=[CH:10][C:8]=3[N:9]=2)[CH2:4][CH2:3][CH2:2]1.Cl.[O:35]1[C:46]2[C:47]3[C:42]([C:43](B(O)O)=[CH:44][CH:45]=2)=[N:41][CH:40]=[CH:39][C:38]=3[CH2:37][CH2:36]1.[F-].[Cs+].C([O-])(O)=O.[Na+]>CC(OC)(C)C.COC1C=CC=C(OC)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].COCCOC>[N:1]1([C:5]2[S:6][C:7]3[C:13]([C:43]4[C:42]5[C:47]6=[C:38]([CH2:37][CH2:36][O:35][C:46]6=[CH:45][CH:44]=4)[CH:39]=[CH:40][N:41]=5)=[C:12]([C@H:22]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:11]([CH3:33])=[CH:10][C:8]=3[N:9]=2)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 516892Sodium BicarbonateHCID 66631384(2,3-Dihydropyrano[4,3,2-de]quinolin-7-yl)boronic acid hydrochlorideHCID 86699784(S)-ethyl 2-(2-(azetidin-1-yl)-5-methyl-7-(trifluoromethylsulfonyloxy)benzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Product 1

HCID 71003367(2S)-ethyl 2-(2-(azetidin-1-yl)-7-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetateYield 52.7%

Reagents, catalysts & solvents 2

HCID 71311105SPhos PalladacycleCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 33 (38 mg, 0.075 mmol) in freshly distilled DME (1 mL) was added 2,3-dihydropyrano[4,3,2-de]quinolin-7-ylboronic acid hydrochloride (24 mg, 0.097 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) methyl-t-butylether adduct, [SPhos Palladacycle] (5 mg, 0.0075 mmol), and cesium fluoride (46 mg, 0.3 mmol). The reaction mixture was heated in the microwave at 110° C. for 45 min. A saturated solution of NaHCO3 (3 mL) was added, and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layer were dried, filtered, and concentrated in vacuo. The crude material was purified by column chromatography (EtOAc/hexanes) to give 21 mg of 34. LCMS-ESI+: calc'd for C30H33N3O4S: 532.2 (M+H+); Found: 532.0 (M+H+).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc
  3. customThe combined organic layer were dried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-aebdbca8e6ae4f1099d313f2a0d7dc88
Source dataset
uspto-grants-2015_08
Patent number
US09096586B2

Reaction notes

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