Methanesulfonyl chloride → HCID 59375020, compound

HRID 1811159Notes

Reaction equation

HRID 1811159 reaction equation
[NH2:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[C:7]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:25](=[O:33])[C:26]5[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=5)[C:19]=4[CH3:34])=[CH:8][CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>C(Cl)Cl.C1COCC1>[F:32][C:29]1[CH:28]=[CH:27][C:26]([C:25]([NH:24][C:20]2[C:19]([CH3:34])=[C:18]([C:7]3[C:6]4[C:5]5[C:13](=[CH:14][C:2]([NH:1][S:36]([CH3:35])(=[O:38])=[O:37])=[CH:3][CH:4]=5)[NH:12][C:11]=4[C:10]([C:15]([NH2:17])=[O:16])=[CH:9][CH:8]=3)[CH:23]=[CH:22][CH:21]=2)=[O:33])=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 59375083HCID 59375083, compound

Product 1

HCID 59375020HCID 59375020, compound

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A solution of 7-amino-4-(3-(4-fluorobenzamido)-2-methylphenyl)-9H-carbazole-1-carboxamide (Example 54-5, 30 mg, 0.066 mmol) and TEA (0.018 mL, 0.133 mmol) in DCM-THF (2:1, 3 mL) was treated with methanesulfonyl chloride (10 μL, 0.133 mmol). The mixture was stirred at rt for 1.5 h, and was concentrated and purified by preparative HPLC to provide 4-(3-(4-fluorobenzamido)-2-methylphenyl)-7-(methylsulfonamido)-9H-carbazole-1-carboxamide as a white solid (Example 59-1, 3.5 mg, 9%). 1H NMR (500 MHz, methanol-d4) δ 7.91-8.01 (2 H, m), 7.83 (1 H, d, J=7.8 Hz), 7.45 (1 H, d, J=1.7 Hz), 7.42 (1 H, d, J=7.8 Hz), 7.34 (1 H, t, J=7.8 Hz), 7.12-7.20 (3 H, m), 6.95 (1 H, d, J=7.8 Hz), 6.88 (1 H, d, J=8.6 Hz), 6.73 (1 H, dd, J=8.5, 2.1 Hz), 2.85 (3 H, s), 1.90 (3 H, s). Mass spectrum m/z 531.0 (M+H)+. Also obtained was 4-(3-(4-fluorobenzamido)-2-methylphenyl)-7-(N-(methylsulfonyl)methylsulfonamido)-9H-carbazole-1-carboxamide as a white solid (Example 59-2, 14 mg, 28%). 1H NMR (400 MHz, DMSO-d6) δ 11.67 (1 H, s), 10.08 (1 H, s), 8.21 (1 H, br. s.), 7.97-8.08 (3 H, m), 7.79 (1 H, d, J=1.8 Hz), 7.53 (1 H, br. s.), 7.48 (1 H, d, J=7.3 Hz), 7.26-7.39 (3 H, m), 7.15 (1 H, d, J=6.5 Hz), 6.93-7.03 (2 H, m), 6.86 (1 H, d, J=8.3 Hz), 3.46 (6 H, d, J=9.0 Hz), 1.86 (3 H, s). Mass spectrum m/z 607.2 (M−H)−.

Workup

  1. concentrationwas concentrated
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-737732a485e74e7799402e921494a957
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

Loading…