Potassium Carbonate → 4-(5-aminonaphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

HRID 661903Notes

Reaction equation

HRID 661903 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[CH:22]=[C:21]3[C:13]([C:14]4[C:15](B5OC(C)(C)C(C)(C)O5)=[CH:16][CH:17]=[C:18]([C:23]([NH2:25])=[O:24])[C:19]=4[NH:20]3)=[CH:12][CH:11]=2)=[O:9])[CH2:4][CH2:3]1.Br[C:36]1[CH:45]=[CH:44][CH:43]=[C:42]2[C:37]=1[CH:38]=[CH:39][CH:40]=[C:41]2[NH2:46].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C>[NH2:46][C:41]1[CH:40]=[CH:39][CH:38]=[C:37]2[C:42]=1[CH:43]=[CH:44][CH:45]=[C:36]2[C:15]1[C:14]2[C:13]3[C:21](=[CH:22][C:10]([C:8]([N:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]4)=[O:9])=[CH:11][CH:12]=3)[NH:20][C:19]=2[C:18]([C:23]([NH2:25])=[O:24])=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 190448935-Bromonaphthalen-1-amineHCID 666059127-(4-methylpiperazine-1-carbonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide

Product 1

HCID 569250334-(5-aminonaphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamideYield 42%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Step 2 A mixture of 7-(4-methylpiperazine-1-carbonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide (the crude product prepared according to Step 1, 40 mg, 0.065 mmol), 5-bromonaphthalen-1-amine (21.61 mg, 0.097 mmol), and potassium carbonate (13.45 mg, 0.097 mmol) in toluene (1.5 mL) and ethanol (0.75 mL) was treated with [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) DCM complex (5.3 mg, 0.007 mmol) and purged with argon for ca. 5 min. The mixture was heated at 90° C. for 19 h, then was cooled to rt and concentrated. The residue was purified by preparative HPLC, then was partitioned between EtOAc and NaHCO3 (aq), the aqueous phase was extracted again with EtOAc, and the combined organic phases were dried and concentrated to provide 4-(5-aminonaphthalen-1-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as a light yellow solid (13.1 mg, 42%). 1H NMR (400 MHz, DMSO-d6) δ 11.71 (s, 1H) 8.22-8.27 (m, 2H) 8.07 (d, J=7.7 Hz, 1H) 7.73 (s, 1H) 7.55 (br. s., 1H) 7.52 (dd, J=8.6, 6.8 Hz, 1H) 7.42 (dd, J=6.9, 1.0 Hz, 1H) 7.09 (d, J=7.7 Hz, 1H) 6.96 (dd, J=8.2, 7.6 Hz, 1H) 6.64-6.70 (m, 2H) 6.49 (d, J=8.3 Hz, 1H) 6.38 (d, J=8.1 Hz, 1H) 5.85 (s, 2H) 3.48-3.59 (m, 4H) 2.17-2.37 (m, 4H) 2.14 (s, 3H). Mass spec m/z 478.10 (M+H)+.

Workup

  1. customprepared
  2. additionwas treated with [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) DCM complex (5.3 mg, 0.007 mmol)
  3. custompurged with argon for ca. 5 min
  4. temperaturewas cooled to rt
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC
  7. customwas partitioned between EtOAc and NaHCO3 (aq)
  8. extractionthe aqueous phase was extracted again with EtOAc
  9. customthe combined organic phases were dried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ee84520ed1264216916e67832dde284e
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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