Water → HCID 66605059, compound

HRID 2410819Notes

Reaction equation

HRID 2410819 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]=[C:13]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=4)[CH:12]=[C:11]([C:25]([NH2:27])=[O:26])[C:7]=3[NH:8][C:9]=2[CH:10]=1.Cl.[CH2:29]([N:36]([CH2:40][CH2:41]Cl)[CH2:37][CH2:38]Cl)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[C:43]([O-:46])([O-])=[O:44].[Na+].[Na+].O>CC(O)(C)C.CO>[C:43]([OH:46])([C:21]([F:24])([F:23])[F:22])=[O:44].[NH3:1].[CH2:29]([N:36]1[CH2:40][CH2:41][N:1]([C:2]2[CH:3]=[CH:4][C:5]3[C:6]4[N:14]=[C:13]([C:15]5[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=5)[CH:12]=[C:11]([C:25]([NH2:27])=[O:26])[C:7]=4[NH:8][C:9]=3[CH:10]=2)[CH2:38][CH2:37]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

9

Reactant 4

HCID 962Water2×HCID 10340Sodium CarbonateHCID 2777881N,N-Bis(2-chloroethyl)benzylamine hydrochlorideHCID 66604922HCID 66604922, compound

Product 3

HCID 222AmmoniaHCID 6422Trifluoroacetic acidYield 0.1%HCID 66605059HCID 66605059, compoundYield 95.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 6386tert-ButanolSolvent

Procedure

A mixture of 7-amino-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (70 mg, 0.189 mmol), N-benzyl-2-chloro-N-(2-chloroethyl)ethanamine hydrochloride (102 mg, 0.378 mmol) and Na2CO3 (100 mg, 0.945 mmol) in t-BuOH (2 mL) was heated at reflux overnight. Preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA, 10-60% B at 42 mL/min over 20 min) and SCX capture and release with 2 N NH3 in MeOH afforded 7-(4-benzylpiperazin-1-yl)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (50 mg, 0.090 mmol, 48% yield). MS (ESI) m/z 530.29 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.33 (1H, s), 8.54-8.64 (3H, m), 8.41 (1H, s), 8.07 (1H, d, J=8.85 Hz), 7.88 (1H, br. s.), 7.72-7.80 (2H, m), 7.35-7.41 (4H, m), 7.26-7.32 (1H, m), 7.22 (1H, d, J=1.83 Hz), 7.01 (1H, dd, J=8.85, 1.83 Hz), 3.57 (2H, s), 3.30 (4H, d, J=3.97 Hz), 2.59 (4H, d, J=3.97 Hz).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight

Sources & evidence

ORD record
ord-ad5b33fb9e3c40cc887afcc31dd6b0a5
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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