4-Fluorobenzoyl chloride → HCID 59375025, compound

HRID 1811090Notes

Reaction equation

HRID 1811090 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[C:22]4[C:21]5[C:16](=[CH:17][C:18]([C:23]([N:25]6[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]6)=[O:24])=[CH:19][CH:20]=5)[NH:15][C:14]=4[C:13]([C:32]([NH2:34])=[O:33])=[CH:12][CH:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[F:35][C:36]1[CH:44]=[CH:43][C:39]([C:40](Cl)=[O:41])=[CH:38][CH:37]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:35][C:36]1[CH:44]=[CH:43][C:39]([C:40]([N:1]2[C:9]3[C:4](=[C:5]([C:10]4[C:22]5[C:21]6[C:16](=[CH:17][C:18]([C:23]([N:25]7[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]7)=[O:24])=[CH:19][CH:20]=6)[NH:15][C:14]=5[C:13]([C:32]([NH2:34])=[O:33])=[CH:12][CH:11]=4)[CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)=[O:41])=[CH:38][CH:37]=1

Participants

5

Reactant 2

HCID 678794-Fluorobenzoyl chloride2×HCID 66606620HCID 66606620, compound

Product 1

HCID 59375025HCID 59375025, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(1H-indol-4-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (Example 3-47, 50 mg, 0.100 mmol) in DCM (1 mL) was treated sequentially with DMAP (3.7 mg, 0.030 mmol), TEA (0.028 mL, 0.199 mmol) and 4-fluorobenzoyl chloride (0.013 mL, 0.110 mmol). The mixture was stirred at rt for 17 h, then was treated with additional 4-fluorobenzoyl chloride (0.013 mL, 0.110 mmol) and TEA (0.028 mL, 0.199 mmol) and stirring was continued for 111 h. The mixture was concentrated and the residue was dissolved in methanol and purified by preparative HPLC. The appropriate effluent fractions were partitioned between NaHCO3 (aq) and EtOAc, and the aqueous phase was extracted twice more with EtOAc. The combined organic phases were dried and concentrated to provide 4-(1-(4-fluorobenzoyl)-1H-indol-4-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as a yellow solid (19.5 mg, 31%). 1H NMR (400 MHz, methanol-d4) δ 8.51 (1H, d, J=8.3 Hz), 8.03 (1H, d, J=7.9 Hz), 7.84 (2H, dd, J=8.8, 5.3 Hz), 7.68 (1H, s), 7.57 (1H, t, J=7.7 Hz), 7.46 (1H, d, J=7.5 Hz), 7.26-7.36 (3H, m), 7.20 (1H, d, J=7.9 Hz), 6.96 (1H, d, J=7.9 Hz), 6.86 (1H, dd, J=8.3, 1.3 Hz), 6.19 (1H, d, J=4.0 Hz), 3.77 (2H, br. s.), 3.46 (2H, br. s.), 2.51 (2H, br. s.), 2.38 (2H, br. s.), 2.30 (3H, s). Mass spectrum m/z 574.3 (M+H)+.

Workup

  1. stirringstirring
  2. waitwas continued for 111 h
  3. concentrationThe mixture was concentrated
  4. dissolutionthe residue was dissolved in methanol
  5. custompurified by preparative HPLC
  6. customThe appropriate effluent fractions were partitioned between NaHCO3 (aq) and EtOAc
  7. extractionthe aqueous phase was extracted twice more with EtOAc
  8. customThe combined organic phases were dried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-42c748a66ffa49d8948b2dc6e741603b
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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