1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 58266482, compound

HRID 1888520Notes

Reaction equation

HRID 1888520 reaction equation
C1(S([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:24]#[N:25])=[C:18]([O:19][CH2:20][CH2:21][O:22][CH3:23])[C:13]=3[C:12]3[CH:26]=[C:27](Br)[CH:28]=[N:29][C:11]2=3)(=O)=O)C=CC=CC=1.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1>[F-].[K+].C(#N)C.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]>[CH3:23][O:22][CH2:21][CH2:20][O:19][C:18]1[C:13]2[C:12]3[CH:26]=[C:27]([C:35]4[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=4)[CH:28]=[N:29][C:11]=3[NH:10][C:14]=2[CH:15]=[N:16][C:17]=1[C:24]#[N:25]

Participants

6

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58266777HCID 58266777, compound

Product 1

HCID 58266482HCID 58266482, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 9-benzenesulfonyl-3-bromo-5-(2-methoxyethoxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (35 mg, 0.07 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (20 mg, 0.096 mmol), [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) (7 mg) in 1N aqueous potassium fluoride solution (0.30 mL) and acetonitrile (0.30 mL) was degassed and heated under microwave irradiation at 130° C. for 30 minutes. The reaction mixture was allowed to cool to ambient temperature and ethyl acetate (5 mL) added. The solid was collected by filtration, washed with water (5 mL) and acetonitrile (5 mL) and left to air dry. The resultant solid was purified by flash chromatography (silica, 500 mg column, Si-SPE, 10% MeOH in DCM) and trituration with acetonitrile (2×0.25 mL) to afford the title compound as a grey solid (12 mg, 50%). 1H NMR (DMSO-D6, 400 MHz): 12.91 (s, 1H), 8.96 (d, J=2.2 Hz, 1H), 8.81 (d, J=2.2 Hz, 1H), 8.77 (s, 1H), 8.27 (s, 1H), 7.98 (s, 1H), 4.66-4.62 (m, 2H), 3.92 (s, 3H), 3.87-3.83 (m, 2H), 3.36 (s, 3H). LCMS (Method A): RT=7.66 min, M+H+=349.

Workup

  1. customwas degassed
  2. temperatureto cool to ambient temperature
  3. additionethyl acetate (5 mL) added
  4. filtrationThe solid was collected by filtration
  5. washwashed with water (5 mL) and acetonitrile (5 mL)
  6. waitleft to air
  7. customdry
  8. customThe resultant solid was purified by flash chromatography (silica, 500 mg column, Si-SPE, 10% MeOH in DCM) and trituration with acetonitrile (2×0.25 mL)

Sources & evidence

ORD record
ord-d24bb0f8caa948aeaabb2229939ae054
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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