Acetyl chloride → HCID 57666425, compound

HRID 1907963Notes

Reaction equation

HRID 1907963 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[NH2:5][O:6][CH2:7][C:8]1[N:9]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:10]2[C:19]3[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=3[N:13]=[C:12]([NH2:20])[C:11]=2[N:21]=1>ClCCl.C(N(CC)CC)C>[NH2:20][C:12]1[C:11]2[N:21]=[C:8]([CH2:7][O:6][NH:5][C:1](=[O:3])[CH3:2])[N:9]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:10]=2[C:19]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=2[N:13]=1

Participants

5

Reactant 2

HCID 6367Acetyl chloride2×HCID 11289248HCID 11289248, compound

Product 1

HCID 57666425HCID 57666425, compoundYield 26.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

A solution of acetyl chloride (0.232 mL, 3.27 mmol) in dichloromethane (10 mL) was added dropwise to a stirred solution of 2-[(aminooxy)methyl]-1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine (prepared as described in Example 123, 860 mg, 2.97 mmol) and triethylamine (1.24 mL, 8.92 mmol) in dichloromethane (20 mL) at 0° C. After 1 hour, additional acetyl chloride (0.232 mL) in dichloromethane (10 mL) and triethylamine (1.0 mL) were added. The reaction mixture was stirred for an additional 30 minutes, then was concentrated under reduced pressure. The crude product was purified by chromatography using a HORIZON HPFC system (silica gel, gradient elution with 5-15% 1 M NH3 in methanol/dichloromethane) followed by crystallization from acetonitrile. The crystals were isolated by filtration, washed with acetonitrile, and dried in a vacuum oven to yield 257 mg of N-{[4-amino-1-(2-methylpropyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-2-yl]methoxy}acetamide as pale yellow crystals, mp 187-188° C.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customThe crude product was purified by chromatography
  3. washa HORIZON HPFC system (silica gel, gradient elution with 5-15% 1 M NH3 in methanol/dichloromethane)
  4. customfollowed by crystallization from acetonitrile
  5. customThe crystals were isolated by filtration
  6. washwashed with acetonitrile
  7. customdried in a vacuum oven

Sources & evidence

ORD record
ord-a009911d524c45908ba016f7190b932b
Source dataset
uspto-grants-2013_12
Patent number
US08598192B2

Reaction notes

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