Water → HCID 71599546, compound

HRID 1622475Notes

Reaction equation

HRID 1622475 reaction equation
F[CH2:2][C:3]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[C:10]=2[CH3:19])[C:6]2[CH:20]=[C:21]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:22]=[C:23]([B:24]([OH:26])[OH:25])[C:5]=2[N:4]=1.C(#N)C.[OH2:36]>>[OH:36][CH2:2][C:3]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:18])[F:17])[C:10]=2[CH3:19])[C:6]2[CH:20]=[C:21]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:22]=[C:23]([B:24]([OH:26])[OH:25])[C:5]=2[N:4]=1

Participants

4

Reactant 3

HCID 962WaterHCID 6342AcetonitrileHCID 71578161HCID 71578161, compound

Product 1

HCID 71599546HCID 71599546, compoundYield 46%

Conditions

Temperature
70 °C

Procedure

(2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid (40 mg, 0.089 mmol) was dissolved in Water+0.1% TFA (2.5 mL) and Acetonitrile+0.1% TFA (2.5 mL) in a 20 mL scintillation vial. The mixture was stirred at 70° C. for 2 days, solution was evaporated and taken up in 50% water/acetonitrile and was purified by reversed phase HPLC eluted with a gradient of acetonitrile (0.1% TFA) and water (0.1% TFA v/v) (20-55%) over 12 minutes. The appropriate fractions were collected and evaporated to yield (2-(hydroxymethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid (18.5 mg, 0.041 mmol, 46.0% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.59 (s, 3H) 3.11-3.21 (m, 4H) 3.75-3.86 (m, 4H) 5.04 (s, 2H) 5.88 (s, 2H) 6.75 (d, 1H) 7.03 (d, J=2.27 Hz, 1H) 7.25 (t, J=7.83 Hz, 1H) 7.65 (d, J=7.83 Hz, 1H) 7.72 (br. s., 1H); LC/MS: MS (ES+) m/e 450 [M+H]+.

Workup

  1. customsolution was evaporated
  2. customwas purified by reversed phase HPLC
  3. washeluted with a gradient of acetonitrile (0.1% TFA) and water (0.1% TFA v/v) (20-55%) over 12 minutes
  4. customThe appropriate fractions were collected
  5. customevaporated

Sources & evidence

ORD record
ord-cfbff1e10d634ecfabf1a0afc2a4251a
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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