Hydrogen Peroxide → HCID 68516867, compound

HRID 2241195Notes

Reaction equation

HRID 2241195 reaction equation
[CH3:1][O:2][C:3]1[CH:44]=[CH:43][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]([C:33]5[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=5)[C:25]([C:27]5([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]5)=[O:26])=[CH:20][C:19]=4[F:40])=[C:11]3[C:10]([CH:41]=[CH2:42])=[N:9]2)=[CH:5][CH:4]=1.B1C2CCCC1CCC2.[OH:54]O>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]([C:33]5[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=5)[C:25]([C:27]5([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]5)=[O:26])=[CH:20][C:19]=4[F:40])=[C:11]3[C:10]([CH2:41][CH2:42][OH:54])=[N:9]2)=[CH:43][CH:44]=1

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 68514661HCID 68514661, compound

Product 1

HCID 68516867HCID 68516867, compoundYield 48.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of N-(4-(1-(4-methoxybenzyl)-3-vinyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.357 g, 0.60 mmol) in THF (5 mL) was added a 0.5 M solution of 9-BBN (3.60 mL, 1.80 mmol) in THF. The reaction was stirred for 18 hours at room temperature. The reaction was cooled in an ice bath, and then was quenched by addition of 2N aqueous NaOH (3 mL). After stirring for 10 minutes in the ice bath, 30% aqueous hydrogen peroxide (0.577 mL, 6.00 mmol) was added. The reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×10 mL). The combined organic phases were washed with brine (20 mL), dried (Na2SO4), filtered, and concentrated. The crude was partially purified by Biotage Flash 40, eluting with 30% EtOAc/hexanes, 1:1 EtOAc/hexanes, 2:1 EtOAc/hexanes, then neat EtOAc. The resulting solid was further purified by preparative TLC, eluting with 5% MeOH (containing 7N NH3) in DCM. The product was obtained as a waxy, white solid (179 mg, 48%). 1H NMR (400 MHz, CDCl3) δ 10.18 (s, 1H), 8.49 (s, 1H), 8.28 (d, J=6 Hz, 1H), 7.75 (m, 1H), 7.46 (m, 2H), 7.32 (d, J=9 Hz, 2H), 7.27 (m, 1H, overlaps chloroform), 7.18 (t, J=9 Hz, 1H), 7.06 (t, J=9 Hz, 2H), 6.83 (d, J=9 Hz, 2H), 6.17 (d, J=6 Hz, 1H), 5.57 (s, 2H), 4.09 (m, 2H), 3.76 (s, 3H), 3.36 (t, J=6 Hz, 2H), 2.76 (s, 1H), 1.80 (m, 2H), 1.63 (m, 2H).

Workup

  1. temperatureThe reaction was cooled in an ice bath
  2. customwas quenched by addition of 2N aqueous NaOH (3 mL)
  3. additionwas added
  4. customThe reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL)
  5. customThe phases were separated
  6. extractionthe aqueous phase was re-extracted with EtOAc (2×10 mL)
  7. washThe combined organic phases were washed with brine (20 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude was partially purified by Biotage Flash 40
  12. washeluting with 30% EtOAc/hexanes, 1:1 EtOAc/hexanes, 2:1 EtOAc/hexanes
  13. customThe resulting solid was further purified by preparative TLC
  14. washeluting with 5% MeOH (containing 7N NH3) in DCM

Sources & evidence

ORD record
ord-8560309435db4a0f8ace942366f2023d
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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