1,2-Dichloroethane → 4-(3-(5-fluoropicolinamido)-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

HRID 1811089Notes

Reaction equation

HRID 1811089 reaction equation
[NH2:1][C:2]1[C:3]([CH3:33])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([C:21]([N:23]5[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]5)=[O:22])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:30]([NH2:32])=[O:31])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[F:34][C:35]1[CH:36]=[CH:37][C:38]([C:41](O)=[O:42])=[N:39][CH:40]=1.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>C(#N)C.CO>[F:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]([NH:1][C:2]2[C:3]([CH3:33])=[C:4]([C:8]3[C:20]4[C:19]5[C:14](=[CH:15][C:16]([C:21]([N:23]6[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]6)=[O:22])=[CH:17][CH:18]=5)[NH:13][C:12]=4[C:11]([C:30]([NH2:32])=[O:31])=[CH:10][CH:9]=3)[CH:5]=[CH:6][CH:7]=2)=[O:42])=[N:39][CH:40]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27628765-fluoropyridine-2-carboxylic AcidHCID 46833813HCID 46833813, compound

Product 1

HCID 593750174-(3-(5-fluoropicolinamido)-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamideYield 96.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(3-amino-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (Example 3-2, 100 mg, 0.204 mmol), 5-fluoropicolinic acid (43.1 mg, 0.306 mmol), and HOAT (41.6 mg, 0.306 mmol) in acetonitrile (2 mL) was treated with DIEA (0.053 mL, 0.306 mmol) and EDC (78 mg, 0.408 mmol) and the mixture was stirred at rt. After 18 h, the mixture was diluted with methanol and purified by preparative HPLC. The aqueous residue from concentration of the appropriate effluent fractions was made basic with NaHCO3 (aq) and extracted three times with EtOAc. The combined organic phases were dried and concentrated to provide 4-(3-(5-fluoropicolinamido)-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as a light gray powder (111.5 mg, 92%). 1H NMR (400 MHz, methanol-d4) δ 8.58 (d, J=3.1 Hz, 1H) 8.31 (dd, J=8.8, 4.8 Hz, 1H) 7.96-8.03 (m, 2H) 7.82 (td, J=8.6, 2.6 Hz, 1H) 7.68 (d, J=0.9 Hz, 1H) 7.45 (t, J=7.9 Hz, 1H) 7.23 (dd, J=7.5, 0.9 Hz, 1H) 7.09 (d, J=7.9 Hz, 1H) 7.03-7.08 (m, 1H) 6.95-7.00 (m, 1H) 3.78 (br. s., 2H) 3.49 (br. s., 2H) 2.52 (br. s., 2H) 2.40 (br. s., 2H) 2.31 (s, 3H) 2.04 (s, 3H). Mass spectrum m/z 565.2 (M+H)+.

Workup

  1. custompurified by preparative HPLC
  2. extractionextracted three times with EtOAc
  3. customThe combined organic phases were dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-d57100172a924318befe3f694e3258f0
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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