Hydrochloric Acid → HCID 59375015, compound

HRID 1811091Notes

Reaction equation

HRID 1811091 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH:6]([NH:9][C:10]1[C:11]([CH3:41])=[C:12]([C:16]2[C:28]3[C:27]4[C:22](=[CH:23][C:24]([C:29]([N:31]5[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]5)=[O:30])=[CH:25][CH:26]=4)[NH:21][C:20]=3[C:19]([C:38]([NH2:40])=[O:39])=[CH:18][CH:17]=2)[CH:13]=[CH:14][CH:15]=1)([CH3:8])[CH3:7].Cl>N1C=CC=CC=1.CO>[CH:6]([N:9]([C:10]1[C:11]([CH3:41])=[C:12]([C:16]2[C:28]3[C:27]4[C:22](=[CH:23][C:24]([C:29]([N:31]5[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]5)=[O:30])=[CH:25][CH:26]=4)[NH:21][C:20]=3[C:19]([C:38]([NH2:40])=[O:39])=[CH:18][CH:17]=2)[CH:13]=[CH:14][CH:15]=1)[S:2]([CH3:1])(=[O:4])=[O:3])([CH3:8])[CH3:7]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chloride2×HCID 59375102HCID 59375102, compound

Product 1

HCID 59375015HCID 59375015, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

Methanesulfonyl chloride (1.3 μL, 0.016 mmol) was added to a stirred solution of 4-(3-(isopropylamino)-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide, TFA salt (Example 9-1, 13 mg, 0.016 mmol) in pyridine (0.2 mL) at rt. After 30 min, additional methanesulfonyl chloride (2.4 μL) was added and the mixture was stirred overnight. The mixture was treated with 1 M hydrochloric acid (0.56 mL), dissolved in methanol and purified by preparative HPLC to provide two rotational isomers of 4-(3-(N-isopropylmethylsulfonamido)-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide, isolated separately as TFA salts after lyophilization. Isomer A (3.3 mg, 31%) 1H NMR (400 MHz, chloroform-d) δ 9.58 (1H, s), 7.81 (1H, d, J=7.70 Hz), 7.68 (1H, s), 7.41-7.47 (1H, m), 7.32-7.37 (2H, m), 7.11 (1H, d, J=7.70 Hz), 7.05 (1H, d, J=8.14 Hz), 6.86 (1H, d, J=8.14 Hz), 4.60-4.72 (1H, m), 3.66 (3H, br. s.), 3.05 (8H, br. s.), 2.90 (3H, s), 1.91 (3H, s), 1.40 (3H, d, J=6.60 Hz), 1.12 (3H, d, J=6.82 Hz). Mass spectrum m/z 562.1 (M+H)+. Isomer B (2.9 mg, 27%) 1H NMR (400 MHz, chloroform-d) δ 9.41 (1H, br. s.), 7.84 (1H, d, J=7.70 Hz), 7.69 (1H, s), 7.46 (1H, t, J=7.81 Hz), 7.36 (2H, t, J=8.25 Hz), 7.13 (1H, d, J=7.70 Hz), 7.05 (1H, dd, J=8.25, 1.21 Hz), 6.92 (1H, d, J=8.36 Hz), 4.71-4.82 (1H, m), 3.67 (3H, br. s.), 2.59-3.07 (11H, m), 1.90 (3H, s), 1.43 (3H, d, J=6.60 Hz), 1.10 (3H, d, J=6.60 Hz). Mass spectrum m/z 562.2 (M+H)+.

Workup

  1. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-b07eea5816a14365b091a0be73b62679
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

Loading…