4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazole → 6-(Isoxazol-4-yl)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1888598Notes

Reaction equation

HRID 1888598 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][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[N:38][O:39][CH:40]=2)O1>C([O-])(=O)C.[K+].C(#N)C.C(Cl)Cl.CO>[O:39]1[CH:40]=[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[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]6)=[CH:17][CH:16]=5)=[CH:14][C:5]=4[C:4]=3[CH:3]=2)[CH:37]=[N:38]1

Participants

7

Reactant 2

HCID 164141804-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazoleHCID 582663876-Bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 1

HCID 445455506-(Isoxazol-4-yl)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleYield 13.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 517044Potassium AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 6-bromo-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (130 mg, 0.18 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (140 mg, 0.74 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (18 mg, 0.002 mmol) in 1N aqueous potassium acetate solution (0.62 mL) and acetonitrile (3 mL) was heated under microwave irradiation at 85° C. for 18 minutes. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by preparative HPLC [0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min] to afford the title compound as a beige solid (10 mg, 10%). 1H NMR (DMSO-D6, 400 MHz): 12.32 (s, 1H), 9.47 (s, 1H), 9.18 (s, 1H), 8.95 (s, 1H), 8.94 (d, J=2.3 Hz, 1H), 8.89 (d, J=2.2 Hz, 1H), 8.68 (s, 1H), 7.76 (d, J=8.1 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 3.50 (s, 2H), 2.37 (s, 4H), 1.52 (m, 4H), 1.41 (m, 2H). LCMS (Method D): RT=6.55 min, M+H+=410.

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (15 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by preparative HPLC [0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min]

Sources & evidence

ORD record
ord-dabaa67d0d6a4068b04c1d78d466980e
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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