Boron tribromide → 2-{4-[1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-ethyl]-benzenesulfonyl}-ethanol

HRID 1515813Notes

Reaction equation

HRID 1515813 reaction equation
C([O:3][CH2:4][CH2:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:23]2[NH:32][C:26]3=[N:27][CH:28]=[C:29]([F:31])[CH:30]=[C:25]3[CH:24]=2)[CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:11][CH:10]=1)(=[O:8])=[O:7])C.B(Br)(Br)Br>ClCCl>[F:31][C:29]1[CH:30]=[C:25]2[CH:24]=[C:23]([CH:15]([C:12]3[CH:13]=[CH:14][C:9]([S:6]([CH2:5][CH2:4][OH:3])(=[O:7])=[O:8])=[CH:10][CH:11]=3)[CH2:16][CH:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[NH:32][C:26]2=[N:27][CH:28]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 672292622-[1-[4-(2-ethoxy-ethanesulfonyl)-phenyl]-2-(tetrahydro-pyran-4-yl)-ethyl]-5-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 532520292-{4-[1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-ethyl]-benzenesulfonyl}-ethanolYield 31.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[1-[4-(2-ethoxy-ethanesulfonyl)-phenyl]-2-(tetrahydro-pyran-4-yl)-ethyl]-5-fluoro-1H-pyrrolo[2,3-b]pyridine (95 mg, 0.2 mmol) in dichloromethane (10 mL) at 0° C. was added a solution of boron tribromide (0.1 ml, 1 mmol) in dichloromethane (10 ml). The mixture was stirred at 0° C. for 1 h. The reaction was quenched with a saturated aqueous sodium bicarbonate solution (20 mL). The mixture was extracted with dichloromethane (2×50 mL), washed with a saturated aqueous sodium bicarbonate solution (3×20 mL) and brine (3×20 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded (2-{4-[1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-ethyl]-benzenesulfonyl}-ethanol (27 mg, 30%) as a white solid: LC/MS m/e calcd for C22H25FN2O4S [M+H]+ 433.52, observed 433.0; 1H NMR (400 MHz, CD3OD) δ ppm 8.00 (t, J=2.1 Hz, 1H), 7.88 (d, J=8.3 Hz, 2H), 7.58-7.66 (m, 3H), 6.41 (s, 1H), 4.43 (t, J=8.0 Hz, 1H), 3.81-3.91 (m, 4H), 3.38 (t, J=6.2 Hz, 2H), 3.24-3.29 (m, 2H), 2.18-2.26 (m, 1H), 2.01 (dt, J=14.0, 7.1 Hz, 1H), 1.70 (t, J=14.1 Hz, 2H), 1.28-1.51 (m, 3H).

Workup

  1. customThe reaction was quenched with a saturated aqueous sodium bicarbonate solution (20 mL)
  2. extractionThe mixture was extracted with dichloromethane (2×50 mL)
  3. washwashed with a saturated aqueous sodium bicarbonate solution (3×20 mL) and brine (3×20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification

Sources & evidence

ORD record
ord-b1e8214b73eb40ff8720ebf48266748b
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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