1,2-Dichloroethane → HCID 59375005, compound

HRID 661924Notes

Reaction equation

HRID 661924 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])=[C:8]2[C:16]=1[NH:15][C:14]1[CH:13]=[C:12]([C:17](O)=[O:18])[CH:11]=[CH:10][C:9]2=1)(=[O:3])[NH2:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:50][N:51]1[CH2:56][CH2:55][CH:54]([NH2:57])[CH2:53][CH2:52]1>C1COCC1.CN(C=O)C>[F:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:7]1[C:8]2[C:9]3[C:14](=[CH:13][C:12]([C:17]([NH:57][CH:54]4[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]4)=[O:18])=[CH:11][CH:10]=3)[NH:15][C:16]=2[C:4]([C:1]([NH2:2])=[O:3])=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 59375023HCID 59375023, compound

Product 1

HCID 59375005HCID 59375005, compoundYield 65.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 8-carbamoyl-5-(2-fluorophenyl)-9H-carbazole-2-carboxylic acid (Example 23-2, 30 mg, 0.086 mmol), EDC (23.11 mg, 0.121 mmol), HOBT (18.46 mg, 0.121 mmol), DIEA (30 μL, 0.172 mmol), and 1-methylpiperidin-4-amine (9.83 mg, 0.086 mmol) in THF and DMF (4:1, 2 mL) was stirred at rt overnight. The mixture was concentrated and purified by preparative HPLC. The isolated product was partitioned between DCM and NaHCO3 (aq). The organic phase was dried and concentrated to provide 4-(2-fluorophenyl)-N7-(1-methylpiperidin-4-yl)-9H-carbazole-1,7-dicarboxamide as a white solid (25 mg, 62%). 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H) 8.24 (br. s., 1H) 8.20 (s, 1H) 8.13 (d, J=7.69 Hz, 1H) 8.05 (d, J=7.91 Hz, 1H) 7.52-7.68 (m, 3H) 7.33-7.48 (m, 3H) 7.13 (d, J=7.69 Hz, 1H) 7.05 (d, J=8.35 Hz, 1H) 3.64-3.80 (m, 1H) 2.69-2.79 (m, 2H) 1.87-2.00 (m, 2H) 1.70-1.80 (m, 2H) 1.48-1.65 (m, 2H). Mass spectrum m/z 445.2 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC
  3. customThe isolated product was partitioned between DCM and NaHCO3 (aq)
  4. customThe organic phase was dried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7c00a63ef34d45ff98571a681ba2da3b
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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