Tetrabutylammonium Fluoride → HCID 68007855, compound

HRID 527012Notes

Reaction equation

HRID 527012 reaction equation
[Si](O[C@@H]1CCC[C@H](NC2C(F)=CN=C(C)C=2C2C3C(=NC=C(Cl)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)[C@H]1O)(C(C)(C)C)(C)C.[Si]([O:52][C@:53]1([CH3:88])[CH2:58][CH2:57][CH2:56][C@H:55]([NH:59][C:60]2[C:65]([F:66])=[CH:64][N:63]=[C:62]([C:67]3[C:75]4[C:70](=[N:71][CH:72]=[C:73]([Cl:76])[CH:74]=4)[N:69](S(C4C=CC(C)=CC=4)(=O)=O)[CH:68]=3)[N:61]=2)[C@H:54]1[OH:87])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(OCC)(=O)C>[Cl:76][C:73]1[CH:74]=[C:75]2[C:67]([C:62]3[N:61]=[C:60]([NH:59][C@H:55]4[CH2:56][CH2:57][CH2:58][C@@:53]([CH3:88])([OH:52])[C@@H:54]4[OH:87])[C:65]([F:66])=[CH:64][N:63]=3)=[CH:68][NH:69][C:70]2=[N:71][CH:72]=1

Participants

6

Reactant 3

HCID 2724141Tetrabutylammonium Fluoride2×HCID 68007206(1R,2R,6S)-2-(tert-butyldimethylsilyloxy)-6-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-2-methylcyclohexanolHCID 68007494(1R,2R,6S)-2-[tert-butyl(dimethyl)silyl]oxy-6-[[2-methyl[5-chloro-1-(p-tolylsulfonyl)-pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyridin-4-yl]amino]cyclohexanol

Product 1

HCID 68007855HCID 68007855, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (1R,2R,6S)-2-[tert-butyl(dimethyl)silyl]oxy-6-[[2-methyl[5-chloro-1-(p-tolylsulfonyl)-pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyridin-4-yl]amino]cyclohexanol, 50f, (0.11 g; 0.16 mmol) in THF (2 mL) at room temperature, was added tetrabutylammonium fluoride (1.5 equiv) and the reaction mixture stirred for 1.5 h, at which point HPLC-analysis revealed no starting material but the de-tosylated product was observed with minor desilylation. An additional equivalent of TBAF was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was suspended in ethyl acetate (10 mL), washed with H2O (2×4 mL), aqueous saturated NH4Cl solution (2 mL) and brine (2 mL). The organic phase was dried (Na2SO4) and concentrated in vacuo to provide 139 mg of crude. The crude residue was purified by reverse phase HPLC (5-95% MeOH/water w/HCl buffer over 15 minutes). to afford 15 mg of desired product, 860. LCMS M+1=392.34

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. washwashed with H2O (2×4 mL), aqueous saturated NH4Cl solution (2 mL) and brine (2 mL)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto provide 139 mg of crude
  6. customThe crude residue was purified by reverse phase HPLC (5-95% MeOH/water w/HCl buffer over 15 minutes)

Sources & evidence

ORD record
ord-7d702aad18dc414f978233a1a4008a24
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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