1-Hydroxybenzotriazole → N-[3-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]isoquinoline-3-carboxamide

HRID 746573Notes

Reaction equation

HRID 746573 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][N:40]1[C:52]2[C:51]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[N:45]=[C:44]([NH2:53])[C:43]=2[N:42]=[C:41]1[CH2:54][CH2:55][CH2:56][CH3:57]>CN1CCCC1=O>[NH2:53][C:44]1[C:43]2[N:42]=[C:41]([CH2:54][CH2:55][CH2:56][CH3:57])[N: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:52]=2[C:51]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[N:45]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 124656Isoquinoline-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 223444131-(3-aminopropyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 23512702N-[3-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]isoquinoline-3-carboxamideYield 75.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

Isoquinoline-3-carboxylic acid (1.05 g, 6.05 mmol) was stirred in 1-methyl-2-pyrrolidinone (50 mL). 1-Hydroxybenzotriazole (885 mg, 6.55 mmol) was added in a single portion. This solution was stirred for 15-20 minutes and then cooled in an ice bath. 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.26 g, 6.55 mmol) was added in small portions over a period of 10 minutes. The solution was stirred for 1 hour and then added dropwise to a solution of 1-(3-aminopropyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine-(1.50 g, 5.04 mmol) in 1-methyl-2-pyrrolidinone (100 mL). After 3 hours the reaction mixture was poured into distilled water (800 mL). A solid precipitated. This material was stirred for 5 hours, isolated by filtration and then air dried over the weekend. The solid was taken up in chloroform (100 mL) and then purified by column chromatography (silica gel eluting sequentially with chloroform (1 L), 1% methanol in chloroform (1 L) and 5% methanol in chloroform (1 L)). The purified material was slurried with hot acetonitrile, cooled, isolated by filtration and then dried in a vacuum oven to provide 1.72 g of N-[3-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]isoquinoline-3-carboxamide as a solid, m.p. 203.8-205.3° C. Analysis: Calculated for C27H28N6O: % C, 71.66; % H, 6.24; % N, 18.57; Found: % C, 71.63; % H, 6.17; % N, 18.57.

Workup

  1. temperaturecooled in an ice bath
  2. stirringThe solution was stirred for 1 hour
  3. additionAfter 3 hours the reaction mixture was poured
  4. distillationinto distilled water (800 mL)
  5. customA solid precipitated
  6. stirringThis material was stirred for 5 hours
  7. customisolated by filtration
  8. customair dried over the weekend
  9. custompurified by column chromatography (silica gel eluting sequentially with chloroform (1 L), 1% methanol in chloroform (1 L) and 5% methanol in chloroform (1 L))
  10. temperaturecooled
  11. customisolated by filtration
  12. customdried in a vacuum oven

Sources & evidence

ORD record
ord-c84502ba8c1842ce871e22c77cee2745
Source dataset
uspto-grants-2008_07
Patent number
US07393859B2

Reaction notes

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