1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 58266694, compound

HRID 1888591Notes

Reaction equation

HRID 1888591 reaction equation
Br[C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH:25]([C:28]([F:31])([F:30])[F:29])[CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.[CH3:32][N:33]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>[CH3:32][N:33]1[CH:37]=[C:36]([C:2]2[N:10]=[CH:9][C:8]3[NH:7][C:6]4[N:11]=[CH:12][C:13]([C:15]5[CH:20]=[CH:19][C:18]([CH2:21][N:22]6[CH2:27][CH2:26][CH:25]([C:28]([F:30])([F:29])[F:31])[CH2:24][CH2:23]6)=[CH:17][CH:16]=5)=[CH:14][C:5]=4[C:4]=3[CH:3]=2)[CH:35]=[N:34]1

Participants

5

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58266798HCID 58266798, compound

Product 1

HCID 58266694HCID 58266694, compoundYield 31.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A degassed mixture of 6-bromo-3-[4-(4-trifluoromethylpiperidin-1-ylmethyl)-phenyl]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (0.15 g, 0.30 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.13 g, 0.60 mmol) and 1,1′-[bis(diphenyl phosphino)ferrocene]dichloropalladium(II)(25 mg, 0.03 mmol) in acetonitrile (3 mL) and saturated aqueous sodium carbonate solution (3 mL) was heated under microwave irradiation at 130° C. for 30 minutes. The cooled reaction mixture was partitioned between DCM and water then separated on a hydrophobic frit. The organic phase was evaporated then the resultant residue was purified by flash chromatography (silica, 12 g column, ISCO, 0-10% methanol in DCM) to afford a residue which was purified by HPLC (C18 column, 50-98% MeCN in water (plus 20 mM triethylamine) to afford the title compound (46 mg, 31%). 1H NMR (DMSO-D6, 400 MHz): 12.15 (s, 1H), 8.94-8.88 (m, 2H), 8.86 (d, J=1.1 Hz, 1H), 8.51 (d, J=1.1 Hz, 1H), 8.21 (s, 1H), 7.99 (d, J=0.8 Hz, 1H), 7.78 (d, J=8.0 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 3.92 (s, 3H), 3.56 (s, 2H), 2.99-2.88 (m, 2H), 2.39-2.19 (m, 1H), 2.00 (t, J=1.5 Hz, 2H), 1.85-1.94 (m, 2H), 1.57-1.38 (m, 2H). LCMS (Method A): RT=5.22 min, M+H+=491.

Workup

  1. customThe cooled reaction mixture
  2. customwas partitioned between DCM and water
  3. customthen separated on a hydrophobic frit
  4. customThe organic phase was evaporated
  5. customthe resultant residue was purified by flash chromatography (silica, 12 g column, ISCO, 0-10% methanol in DCM)
  6. customto afford a residue which
  7. customwas purified by HPLC (C18 column, 50-98% MeCN in water (plus 20 mM triethylamine)

Sources & evidence

ORD record
ord-450c4065f88f4d0d8762479487c77730
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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