Sodium Bicarbonate → {3-[4-[1-ethyl-3-(4-nitrophenyl)-1H-pyrazol-4-yl]-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanol

HRID 1727740Notes

Reaction equation

HRID 1727740 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C:9]([C:11]3[CH:12]=[C:13]([CH2:17][OH:18])[CH:14]=[CH:15][CH:16]=3)=[CH:10][C:3]=12.[CH2:28]([N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[C:32]([C:44]2[CH:49]=[CH:48][C:47]([N+:50]([O-:52])=[O:51])=[CH:46][CH:45]=2)=[N:31]1)[CH3:29].C([O-])(O)=O.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH2:28]([N:30]1[CH:34]=[C:33]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[N:8]([S:19]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)(=[O:21])=[O:20])[C:9]([C:11]4[CH:12]=[C:13]([CH2:17][OH:18])[CH:14]=[CH:15][CH:16]=4)=[CH:10][C:3]=23)[C:32]([C:44]2[CH:49]=[CH:48][C:47]([N+:50]([O-:52])=[O:51])=[CH:46][CH:45]=2)=[N:31]1)[CH3:29]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 58980081{3-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanolHCID 689953481-ethyl-3-(4-nitrophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 58980030{3-[4-[1-ethyl-3-(4-nitrophenyl)-1H-pyrazol-4-yl]-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanolYield 90%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a large pressure bottle (˜1 L) was added {3-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl}methanol (22.75 g, 51.3 mMol), 1-ethyl-3-(4-nitrophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (21.0 g of a ˜85% pure lot, 52.0 mMol, Intermediate 5), dioxane (400 mL), aq. sat. NaHCO3 (120 mL), and Pd(PPh3)4 (1.5 g, 1.3 mMol). The reaction was purged with N2, capped, and stirred at 110° C. for 16 h. After cooling to RT the reaction was concentrated under vacuum, taken up in EtOAc, washed with H2O, brine, dried (Mg2SO4), filtered, and evaporated to dryness under vacuum. Purification by flash chromatography by silica gel (20 to 30% EtOAc/CH2Cl2) gave the title compound (26.90 g, 90%) as a yellow solid: MS (ES) m/e 580.4 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.32 (d, J=5.1 Hz, 1H), 8.15 (app. d, 2H), 7.89 (d, J=7.3 Hz, 2H), 7.74 (t, J=7.5 Hz, 1H), 7.61 (app. t, J=7.8 Hz, 2H), 7.54 (app. d, 2H), 7.39-7.43 (m, 2H), 7.32-7.36 (m, 2H), 7.06 (d, J=5.1 Hz, 1H), 6.52 (s, 1H), 5.31 (t, J=5.6 Hz, 1H), 4.57 (d, J=5.3 Hz, 2H), 4.26 (q, J=7.2 Hz, 2H), 1.47 (t, J=7.3 Hz, 3H).

Workup

  1. customThe reaction was purged with N2
  2. customcapped
  3. temperatureAfter cooling to RT the reaction
  4. concentrationwas concentrated under vacuum
  5. washwashed with H2O, brine
  6. dry with materialdried (Mg2SO4)
  7. filtrationfiltered
  8. customevaporated to dryness under vacuum
  9. customPurification by flash chromatography by silica gel (20 to 30% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-e2462a3d1f504cc08b9fcef935b0400c
Source dataset
uspto-grants-2009_02
Patent number
US07495102B2

Reaction notes

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