1-(Aminomethyl)cyclohexan-1-ol → 1-[(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]cyclobutanol

HRID 44765

Reaction equation

HRID 44765 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-])=O.Cl[C:16]1C2C(=NC=CC=2)N=C[C:17]=1[N+]([O-])=O.[NH2:29][CH2:30][C:31]1([OH:35])[CH2:34][CH2:33][CH2:32]1.[NH2:36]CC1(O)CCCCC1.CC(C)(C)C([O-])([O-])[O-].COC(OC)(OC)CCC>>[NH2:36][C:4]1[C:3]2[N:12]=[C:16]([CH3:17])[N:29]([CH2:30][C:31]3([OH:35])[CH2:34][CH2:33][CH2:32]3)[C:2]=2[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:5]=1

Participants

7

Reactant 6

HCID 776141-(Aminomethyl)cyclohexan-1-olHCID 1235121,1,1-TrimethoxybutaneHCID 112758084-Chloro-3-nitroquinolineHCID 125432134-Chloro-3-nitronaphthyridineHCID 21927715TrimethylorthoacetateHCID 282600091-(Aminomethyl)cyclobutan-1-ol

Product 1

HCID 575155171-[(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]cyclobutanol

Conditions

Temperature
90 °C

Procedure

1-[(4-Amino-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]cyclobutanol was prepared according to the general methods of Example 57 using 4-chloro-3-nitroquinoline in lieu of 4-chloro-3-nitronaphthyridine and 1-(aminomethyl)cyclobutanol in lieu of 1-(aminomethyl)cyclohexanol in Part A and trimethylorthoacetate in lieu of trimethylorthobutyrate in Part C. The crude product was triturated sequentially with ethyl acetate, hot chloroform, and acetonitrile, purified by HPFC eluting with a gradient of 0-40% CMA in chloroform, and then suspended in water (100 mL). Concentrated hydrochloric acid (2 mL) was added and the mixture was heated to 90° C. The hot solution was made basic (pH 10) with solid sodium bicarbonate. The solution was allowed to cool to ambient temperature. A precipitate was isolated by filtration, washed well with water, and then dried to provide pure product as a white powder, mp>250.0° C. Anal. Calcd for C16H18N4O C, 68.06; H, 6.43; N, 19.84. Found: C, 67.99; H, 6.54; N, 19.81.

Workup

  1. customThe crude product was triturated sequentially with ethyl acetate, hot chloroform, and acetonitrile
  2. custompurified by HPFC
  3. washeluting with a gradient of 0-40% CMA in chloroform
  4. additionConcentrated hydrochloric acid (2 mL) was added
  5. temperatureto cool to ambient temperature
  6. customA precipitate was isolated by filtration
  7. washwashed well with water
  8. customdried
  9. customto provide pure product as a white powder, mp>250.0° C

Sources & evidence

ORD record
ord-101543d26e62459fa2ee7f0edc5d0859
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Linked notes

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