1-Hydroxybenzotriazole → HCID 23512726, compound

HRID 353882Notes

Reaction equation

HRID 353882 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([OH:13])=O)[N:2]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:36][CH2:37][CH2:38][CH2:39][CH2:40][N:41]1[C:53]2[C:52]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[N:46]=[C:45]([NH2:54])[C:44]=2[N:43]=[C:42]1[CH2:55][CH2:56][O:57][CH3:58]>ClCCl.N1C=CC=CC=1>[NH2:54][C:45]1[C:44]2[N:43]=[C:42]([CH2:55][CH2:56][O:57][CH3:58])[N:41]([CH2:40][CH2:39][CH2:38][CH2:37][NH:36][C:11]([C:3]3[N:2]=[CH:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)=[O:13])[C:53]=2[C:52]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[N:46]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 124656Isoquinoline-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 221808721-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 23512726HCID 23512726, compoundYield 29.6%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere isoquinoline-3-carboxylic acid (1.32 g, 7.63 mmol), 1-hydroxybenzotriazole (1.12 g, 8.27 mmol), and dichloromethane (60 mL) were combined, allowed to stir for several minutes and then cooled to 0° C. 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride was added. Pyridine (1.8 mL) was added and the resulting mixture was allowed to stir for at least 60 minutes. A solution of 1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine (2.0 g, 6.37 mmol) in dichloromethane (250 mL) was added dropwise. The reaction mixture was allowed to stir at ambient temperature overnight. The reaction mixture was washed with sodium bicarbonate, dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The crude material was purified by column chromatography (40 g silica gel eluting with dichloromethane/methanol 9/1) followed by recrystallization from methanol to provide 882 mg of N-{4-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}isoquinoline-3-carboxamide as a yellow crystalline solid, m.p. 199-200° C. Analysis: Calculated for C27H28N6O2: % C, 69.21; % H, 6.02; % N, 17.94. Found: % C, 69.03; % H, 5.99; % N, 18.11.

Workup

  1. stirringto stir for at least 60 minutes
  2. stirringto stir at ambient temperature overnight
  3. washThe reaction mixture was washed with sodium bicarbonate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by column chromatography (40 g silica gel eluting with dichloromethane/methanol 9/1)
  8. customfollowed by recrystallization from methanol

Sources & evidence

ORD record
ord-856d15b83b474fbb81d4685a69526d06
Source dataset
uspto-grants-2004_06
Patent number
US06756382B2

Reaction notes

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