Tetrabutylammonium Fluoride → (1H-benzo[d]imidazol-2-yl)(3-(3-(4-hydroxycyclohex-1-enyl)pyrazin-2-yloxy)azetidin-1-yl)methanone

HRID 2207835Notes

Reaction equation

HRID 2207835 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]1[CH2:15][CH:14]([O:16][C:17]2[C:22]([C:23]3[CH2:28][CH2:27][CH:26]([O:29][Si](C(C)(C)C)(C)C)[CH2:25][CH:24]=3)=[N:21][CH:20]=[CH:19][N:18]=2)[CH2:13]1)=[O:11].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]1[CH2:13][CH:14]([O:16][C:17]2[C:22]([C:23]3[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25][CH:24]=3)=[N:21][CH:20]=[CH:19][N:18]=2)[CH2:15]1)=[O:11]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 58547772HCID 58547772, compound

Product 1

HCID 58548099(1H-benzo[d]imidazol-2-yl)(3-(3-(4-hydroxycyclohex-1-enyl)pyrazin-2-yloxy)azetidin-1-yl)methanoneYield 28.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (1H-benzo[d]imidazol-2-yl)(3-(3-(4-(tert-butyldimethylsilyloxy)cyclohex-1-enyl)pyrazin-2-yloxy)azetidin-1-yl)methanone (336 mg, 0.664 mmol) and THF (6 mL) was added 1M TBAF in THF (1.6 mL, 1.600 mmol). After 24 hours, the reaction solution was eluted through a short plug of silica gel. The filtrate was concentrated in vacuo and adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 0% to 4% MeOH in DCM, to provide (1H-benzo[d]imidazol-2-yl)(3-(3-(4-hydroxycyclohex-1-enyl)pyrazin-2-yloxy)azetidin-1-yl)methanone (75 mg, 28.8% yield), as a light yellow solid. MS (ESI) m/z 392.1 (MH+). IC50 (uM) 0.07168. 1H NMR (CDCl3, 400 MHz) δ (ppm): 1.63-1.67 (m, 1H), 1.77-1.87 (m, 1H), 2.00-2.07 (m, 1H), 2.26-2.35 (m, 1H), 2.60-2.71 (m, 2H), 2.74-2.84 (m, 1H), 4.07-4.13 (m, 1H), 4.33 (dd, 1H, J=11.74 Hz, 4.11 Hz), 4.71 (dd, 1H, J=11.74 Hz, 6.65 Hz), 4.90 (dd, 1H, J=11.93 Hz, 4.11 Hz), 5.31 (dd, 1H, J=11.93 Hz, 6.65 Hz), 5.52-5.58 (m, 1H), 6.76 (br s, 1H), 7.29-7.41 (m, 2H), 7.54 (d, 1H, J=7.82 Hz), 7.82 (d, 1H, J=8.02 Hz), 7.93 (d, 1H, J=2.54 Hz), 8.19 (d, 1H, J=2.54 Hz), 10.59 (s, 1H).

Workup

  1. washthe reaction solution was eluted through a short plug of silica gel
  2. concentrationThe filtrate was concentrated in vacuo
  3. customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
  4. washeluting with 0% to 4% MeOH in DCM

Sources & evidence

ORD record
ord-5107b1e448dd4efa8a21979b2841bd10
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

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