Water → HCID 18405528, compound

HRID 1018345Notes

Reaction equation

HRID 1018345 reaction equation
[C:1]12([CH2:11][CH2:12][C:13]3[NH:17][C:16]([C:18]4([CH2:24][O:25]C)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[N:15][C:14]=3[C:27]([NH:29][C:30]3[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=3)[C:33]([OH:35])=[O:34])=[O:28])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.B(Br)(Br)Br.O>C(Cl)Cl>[C:1]12([CH2:11][CH2:12][C:13]3[NH:17][C:16]([C:18]4([CH2:24][OH:25])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]4)=[N:15][C:14]=3[C:27]([NH:29][C:30]3[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=3)[C:33]([OH:35])=[O:34])=[O:28])[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2

Participants

5

Reactant 3

HCID 962WaterHCID 25134Boron tribromideHCID 18405358HCID 18405358, compound

Product 1

HCID 18405528HCID 18405528, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 3-{[5-(2-adamantan-1-yl-ethyl)-2-(1-methoxymethyl-cyclohexyl)-1H-imidazole-4-carbonyl]-amino}-benzoic acid (Example 203) (300 mg, 0.58 mmol) in DCM (10 ml) was added 1 M solution of boron tribromide in DCM (1.72 ml, 1.72 mmol) at 0° C. The mixture was stirred at room temperature for 16 h, cooled to 0° C., and water (20 ml) was added slowly. The product was extracted with DCM/MeOH (3×20 ml of 9:1 mixture), the organic phase was dried (MgSO4) and the solvent was evaporated. The crude product was purified by flash column chromatography (silica, DCM/MeOH, 95:5) to afford the title compound as a white solid (40.5 mg, 14%). 1H NMR (300 MHz, d6-DMSO) 9.51 (1H, s), 8.38 (1H, s), 7.92 (1H, d), 7.60 (1H, d), 7.40 (1H, t), 3.41 (2H, s), 2.87 (2H, m), 2.05 (2H, m), 1.94 (3H, br s), 1.65 (6H, m), 1.52 (11H, m), 1.34 (5H, m). The acid was converted to the N-methyl-D-glucamine salt and lyophilised from water/dioxan. Found: C, 60.86; H, 8.33; N, 7.76%. C37H56N4O9.1.6 H2O requires: C, 60.86; H, 8.18; N, 7.67%.

Workup

  1. temperaturecooled to 0° C.
  2. extractionThe product was extracted with DCM/MeOH (3×20 ml of 9:1 mixture)
  3. dry with materialthe organic phase was dried (MgSO4)
  4. customthe solvent was evaporated
  5. customThe crude product was purified by flash column chromatography (silica, DCM/MeOH, 95:5)

Sources & evidence

ORD record
ord-39c6e4b0df304726a64792fac226e443
Source dataset
uspto-grants-2002_11
Patent number
US06479531B1

Reaction notes

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