2-(2-Chloroethoxy)acetyl chloride → HCID 86663056, compound

HRID 2410832Notes

Reaction equation

HRID 2410832 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]=[C:13]([Br:15])[CH:12]=[C:11]([C:16]([NH2:18])=[O:17])[C:7]=3[NH:8][C:9]=2[CH:10]=1.[Cl:19][CH2:20][CH2:21][O:22][CH2:23][C:24](Cl)=[O:25]>C1(C)C=CC=CC=1>[Br:15][C:13]1[CH:12]=[C:11]([C:16]([NH2:18])=[O:17])[C:7]2[NH:8][C:9]3[CH:10]=[C:2]([NH:1][C:24](=[O:25])[CH2:23][O:22][CH2:21][CH2:20][Cl:19])[CH:3]=[CH:4][C:5]=3[C:6]=2[N:14]=1

Participants

4

Reactant 2

HCID 190484202-(2-Chloroethoxy)acetyl chlorideHCID 86663054HCID 86663054, compound

Product 1

HCID 86663056HCID 86663056, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-amino-2-bromo-5H-pyrido[3,2-b]indole-4-carboxamide (200 mg, 0.655 mmol) and 2-(2-chloroethoxy)acetyl chloride (113 mg, 0.721 mmol) in toluene (1.5 mL) was stirred at 100° C. for 12 hr. The solvent was removed and 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) followed by SCX capture and release with 2 N NH3 in MeOH left 2-bromo-7-(2-(2-chloroethoxy)acetamido)-5H-pyrido[3,2-b]indole-4-carboxamide (80 mg, 0.19 mmol, 29% yield) as a yellow solid. MS (ESI) m/z 426.97 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.73 (1H, s), 9.99 (1H, s), 8.44 (1H, br. s.), 8.24 (1H, s),8.09 (1H, d, J=8.55 Hz), 7.98 (1H, s), 7.91 (1H, br. s.), 7.49 (1H, d, J=9.46 Hz), 4.21 (2H, s), 3.86 (4H, s).

Workup

  1. customThe solvent was removed
  2. custompreparative 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)

Sources & evidence

ORD record
ord-d6498bfb473641b392600b398202f972
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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