Boron tribromide → HCID 57557276, compound

HRID 81912Notes

Reaction equation

HRID 81912 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21]CC)[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:24][CH2:25][C:26]3[N:27]=[CH:28][S:29][CH:30]=3)=[CH:5][C:4]=2[N:3]=1.B(Br)(Br)Br>ClCCl.Cl.C(Cl)(Cl)Cl>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][OH:21])[N:14]([CH2:15][C:16]([CH3:17])([OH:18])[CH3:19])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:24][CH2:25][C:26]3[N:27]=[CH:28][S:29][CH:30]=3)=[CH:5][C:4]=2[N:3]=1

Participants

6

Reactant 2

HCID 25134Boron tribromideHCID 575453141-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

Product 1

HCID 57557276HCID 57557276, compoundYield 48.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×

Procedure

Under a nitrogen atmosphere, a solution of 1-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (400 mg, 0.94 mmol, which can be prepared as described in International Application No. PCT/US04/28021 Example 137) in dichloromethane (50 mL) was cooled to 0° C. in an ice bath. A solution to of boron tribromide in dichloromethane (3.76 mL of 1.0 M) was added slowly. The reaction mixture was allowed to slowly warm to ambient temperature overnight. The reaction mixture was diluted with hydrochloric acid (20 mL of 6 N) and stirred for 30 minutes. The layers were separated. The organic layer was washed with 6 N hydrochloric acid (3×20 mL) and then discarded. The aqueous layer was made basic by the addition of solid potassium carbonate. A precipitate was isolated by filtration, dissolved in hot chloroform, and then purified by prep HPLC (HORIZON HPFC system eluting with 0-10% CMA in chloroform over 192 mL and then with 10-40% CMA in chloroform over 1400 mL) to provide a solid. This material was crystallized from acetonitrile to provide 181 mg of 1-[4-amino-2-hydroxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a white solid, mp 260-262° C. Anal. calcd for C19H21N5O3S: % C, 56.81; % H, 5.41; % N, 17.26. Found: % C, 56.82; % H, 5.54; % N, 17.23.

Workup

  1. customThe layers were separated
  2. washThe organic layer was washed with 6 N hydrochloric acid (3×20 mL)
  3. additionThe aqueous layer was made basic by the addition of solid potassium carbonate
  4. customA precipitate was isolated by filtration
  5. custompurified by prep HPLC (HORIZON HPFC system
  6. washeluting with 0-10% CMA in chloroform over 192 mL
  7. customwith 10-40% CMA in chloroform over 1400 mL) to provide a solid
  8. customThis material was crystallized from acetonitrile

Sources & evidence

ORD record
ord-59721607905f4293a8c6226cfa10cf45
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Reaction notes

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