Sodium Carbonate → HCID 49869929, compound

HRID 571958Notes

Reaction equation

HRID 571958 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1.Br[C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:25][C@H:26]2[CH2:31][CH2:30][CH2:29][C@@H:28]([N:32]3[CH:36]=[N:35][N:34]=[CH:33]3)[CH2:27]2)(=[O:24])=[O:23])=[C:18]([CH2:37][CH3:38])[CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:37]([C:18]1[CH:17]=[C:16]([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:14])([F:13])[F:1])=[CH:5][CH:6]=2)[CH:21]=[CH:20][C:19]=1[S:22]([NH:25][C@H:26]1[CH2:31][CH2:30][CH2:29][C@@H:28]([N:32]2[CH:36]=[N:35][N:34]=[CH:33]2)[CH2:27]1)(=[O:24])=[O:23])[CH3:38]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 49869930HCID 49869930, compound

Product 1

HCID 49869929HCID 49869929, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (336 mg, 0.411 mmol) was added to a stirred solution of 4-(trifluoromethoxy)phenylboronic acid (1.27 g, 6.17 mmol), 2a (1.70 g, 4.11 mmol) and sodium carbonate (5.14 mL of a 2.0 M aqueous solution) in ethanol (32.0 mL) and toluene (8.0 mL). The resulting mixture was degassed and heated to 90° C. After 3 h, the reaction mixture was cooled to rt and filtered through a short column of Celite, eluting copiously with EtOH. The combined organics were concentrated in vacuo, and the crude residue was purified by column chromatography on silica gel (gradient elution, 1-9% MeOH/DCM as eluent), yielding a brown solid that was subsequently purified by reversed phase HPLC on YMC Pack Pro C18 phase (gradient elution; 10%-70% acetonitrile/water as eluent, 0.05% TFA modifier) to afford the title compound 2b. m/z (ES) 495 (MH)+. 1HNMR (500 MHz, CD3OD) δ 9.45 (s, 1H), 8.03 (d, 1H, J=1.7 Hz), 7.78 (d, 2H, J=3.3 Hz), 7.70 (d, 1H, J=0.3 Hz), 7.66 (dd, 1H, J=1.5, 3.5 Hz), 7.39 (d, 2H, J=1.7 Hz), 4.15 (m, 1H), 3.13 (m, 2H), 2.55 (d, 1H, J=2.3 Hz), 2.15 (d, 1H, 2.4 Hz), 1.60-1.90 (m, 6H), 1.23 (m, 6H). IC50=3.6 nM

Workup

  1. customThe resulting mixture was degassed
  2. temperaturethe reaction mixture was cooled to rt
  3. filtrationfiltered through a short column of Celite
  4. washeluting copiously with EtOH
  5. concentrationThe combined organics were concentrated in vacuo
  6. customthe crude residue was purified by column chromatography on silica gel (gradient elution, 1-9% MeOH/DCM as eluent)
  7. customyielding a brown solid that
  8. customwas subsequently purified by reversed phase HPLC on YMC Pack Pro C18 phase (gradient elution; 10%-70% acetonitrile/water as eluent, 0.05% TFA modifier)

Sources & evidence

ORD record
ord-896f632e82cb4a4192f83d64b2e223f5
Source dataset
uspto-grants-2015_05
Patent number
US09029377B2

Reaction notes

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