Sodium Carbonate → 4-(7-fluoro-1H-indol-6-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

HRID 661904Notes

Reaction equation

HRID 661904 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[C:44]([F:45])=[C:43]2[C:39]([CH:40]=[CH:41][NH:42]2)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:45][C:44]1[C:36]([C:15]2[C:14]3[C:13]4[C:21](=[CH:22][C:10]([C:8]([N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[O:9])=[CH:11][CH:12]=4)[NH:20][C:19]=3[C:18]([C:23]([NH2:25])=[O:24])=[CH:17][CH:16]=2)=[CH:37][CH:38]=[C:39]2[C:43]=1[NH:42][CH:41]=[CH:40]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 591331976-Bromo-7-fluoro-1H-indoleHCID 666059127-(4-methylpiperazine-1-carbonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide

Product 1

HCID 468340984-(7-fluoro-1H-indol-6-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamideYield 30%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7-(4-methylpiperazine-1-carbonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide (prepared according to the procedure of Step 1 of Example 2-1, 75 mg, 0.065 mmol), 6-bromo-7-fluoro-1H-indole (prepared according to U.S. pat. appl. 2007/112005, 18.7 mg, 0.087 mmol), and 2 M aqueous sodium carbonate (0.081 mL, 0.162 mmol) in toluene (0.8 mL) and ethanol (0.2 mL) was purged with argon, treated with tetrakis(triphenylphosphine)palladium (7.5 mg, 0.007 mmol) and heated at 90° C. After 16 h, the mixture was cooled to rt. The residue was purified by preparative HPLC. The resulting TFA salt was partitioned between NaHCO3 (aq) and EtOAc, and the organic extracts were dried and concentrated to provide 4-(7-fluoro-1H-indol-6-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as an off-white solid (9 mg, 30%). 1H NMR (400 MHz, methanol-d4) δ 7.99 (d, J=7.5 Hz, 1H) 7.68 (d, J=0.9 Hz, 1H) 7.52 (d, J=7.9 Hz, 1H) 7.39 (d, J=3.5 Hz, 1H) 7.25 (dd, J=8.1, 1.1 Hz, 1H) 7.21 (d, J=7.5 Hz, 1H) 7.08 (dd, J=8.1, 6.4 Hz, 1H) 6.92 (dd, J=8.1, 1.5 Hz, 1H) 6.63 (t, J=3.3 Hz, 1H) 3.77 (br. s., 2H) 3.49 (br. s., 2H) 2.51 (br. s., 2H) 2.39 (br. s., 2H) 2.30 (s, 3H). Mass spectrum m/z 470.1 (M+H)+.

Workup

  1. customprepared
  2. customwas purged with argon
  3. temperaturethe mixture was cooled to rt
  4. customThe residue was purified by preparative HPLC
  5. customThe resulting TFA salt was partitioned between NaHCO3 (aq) and EtOAc
  6. customthe organic extracts were dried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1e1ef790dac844a78fa796852ff35409
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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