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

HRID 1506059Notes

Reaction equation

HRID 1506059 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[O:40][CH:39]=[N:38][CH:37]=2)O1>C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.C(Cl)Cl.CO>[O:40]1[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:16]=[CH:17][C:18]([CH2:21][N:22]6[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]6)=[CH:19][CH:20]=5)=[CH:14][C:5]=4[C:4]=3[CH:3]=2)=[CH:37][N:38]=[CH:39]1

Participants

7

Reactant 2

HCID 534270915-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-oxazoleHCID 582663876-Bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 1

HCID 582665796-(Oxazol-5-yl)-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleYield 29%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 6-bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (150 mg, 0.36 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxazole (140 mg, 0.71 mmol), 1,1′-[bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (29 mg, 0.004 mmol) in saturated aqueous sodium carbonate solution (0.5 mL) and acetonitrile (5 mL) was heated under microwave irradiation at 130° C. for 30 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 [20-60% MeCN in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min] to afford the title compound as an off-white solid (42 mg, 29%). 1H NMR (DMSO-D6, 400 MHz): 12.42 (s, 1H), 9.12 (d, J=2.2 Hz, 1H), 8.96 (s, 1H), 8.94 (d, J=2.2 Hz, 1H), 8.67 (s, 1H), 8.52 (s, 1H), 7.78 (d, J=8.1 Hz, 2H), 7.66 (s, 1H), 7.44 (d, J=8.1 Hz, 2H), 3.50 (s, 2H), 2.37 (s, 4H), 1.51 (m, 4H), 1.40 (m, 2H). LCMS (Method D): RT=7.76 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 [20-60% MeCN in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min]

Sources & evidence

ORD record
ord-8c7e95ea016a463f9c7eac7f150558c1
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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