Hydrochloric Acid → HCID 178428863, compound

HRID 1798241Notes

Reaction equation

HRID 1798241 reaction equation
C([O:3][C:4](=[O:26])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[C:20]([C:24]#[N:25])[N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)C.Cl.[CH2:28]([NH2:32])[CH:29]([CH3:31])[CH3:30]>CO>[OH:11][B:9]1[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[N:22][CH:21]=[C:20]([C:24](=[NH:25])[NH:32][CH2:28][CH:29]([CH3:31])[CH3:30])[N:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]=2[CH:6]([CH2:5][C:4]([OH:3])=[O:26])[O:10]1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 6558IsobutylamineHCID 67252450HCID 67252450, compound

Product 1

HCID 178428863HCID 178428863, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of [6-(6-cyano-pyrazin-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (200 mg, 0.57 mmol) in methanol (4.7 mL) was bubbled through gaseous HCl for 40 minutes at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 4 h. The solvent was removed under reduced pressure. To the residue was added methanol (2.5 mL) and ammonia solution (28%, 0.27 mL). The reaction mixture was refluxed for overnight. LC-MS showed all material converted to methyl imidate while the ethyl ester group was also hydrolyzed to free acid. The solvent was removed under reduced pressure. Half of the residue (0.28 mmol) was dissolved in methanol (2 mL) and isobutylamine (0.29 mL, 2.9 mmol) was added. The reaction mixture was refluxed overnight. The pH was adjusted to pH 3 with aqueous HCl (6 N). Prep-HPLC separation (C18 column) gave the title compound (11 mg, 10%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 8.90 (1H, s), 8.58 (1H, s), 7.25 (1H, s), 7.14 (1H, s), 5.65 (1H, dd), 3.15 (1H, m), 3.02 (2H, m), 2.60 (3H, s), 2.30 (1H, m), 1.78 (1H, m), 0.95 (3H, d), 0.94 (3H, d). MS found (electrospray): (M+H)+=399.2.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionTo the residue was added methanol (2.5 mL) and ammonia solution (28%, 0.27 mL)
  3. temperatureThe reaction mixture was refluxed for overnight
  4. customThe solvent was removed under reduced pressure
  5. temperatureThe reaction mixture was refluxed overnight
  6. customPrep-HPLC separation (C18 column)

Sources & evidence

ORD record
ord-2a2d762dde3c4e3c83f9182319139aab
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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