Hydrochloric Acid → HCID 10254044, compound

HRID 1354658Notes

Reaction equation

HRID 1354658 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:47])[CH2:9][NH:10][C:11]2[CH2:15][N:14](S(C(F)(F)F)(=O)=O)[C:13](=[O:23])[C:12]=2[C:24]2[N:28](C(OC(C)(C)C)=O)[C:27]3[CH:36]=[C:37]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[CH:38]=[C:39]([CH3:40])[C:26]=3[N:25]=2)[CH:5]=[CH:6][CH:7]=1.O.ClCCl.Cl>CN(C)C=O.C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:47])[CH2:9][NH:10][C:11]2[CH2:15][NH:14][C:13](=[O:23])[C:12]=2[C:24]2[NH:28][C:27]3[CH:36]=[C:37]([N:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)[CH:38]=[C:39]([CH3:40])[C:26]=3[N:25]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 6344DichloromethaneHCID 58666633HCID 58666633, compound

Product 1

HCID 10254044HCID 10254044, compoundYield 138.9%

Reagents, catalysts & solvents 2

HCID 516892Sodium BicarbonateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of (S)-4-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-3-(1-tert-butyloxycarbonyl-4-methyl-6-morpholin-4-yl-1H-benzoimidazol-2-yl)-1-trifluoromethanesulfonyl-1,5-dihydro-pyrrol-2-one (0.014 g, 0.020 mmol) in N,N-dimethylformamide (2 mL) was added saturated sodium bicarbonate (10 drops) and this was heated at 80° C. for 6 hours. The reaction was cooled down to RT and water and dichloromethane were added. The pH of the aqueous phase was adjusted to 7 with 0.5 N hydrochloric acid. The aqueous phase was extracted with dichloromethane (5×). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue (0.012 g) was dissolved in dichloromethane (1.5 mL) and treated with SCX resin (0.750 g). This mixture was stirred at RT for 2 hours, then the resin was washed with dichloromethane, followed by ammonia (2N in methanol, diluted with dichloromethane (3 parts)). The ammonia solution was evaporated to give a residue (0.013 g) which was purified by Prep HPLC (acetonitrile/ammonium acetate/water) and afforded the acetic acid salt of the title material (0.0054 g, 51%) as a beige solid. HPLC: 95% (220 nm), LCMS (+ESI, M+H+) m/z 468, HRMS calcd for C24H26N5O3Cl=467.1724, found: 467.1715; IR ν (cm−1): 3382, 2922, 1636, 1597. 1H NMR (400 MHz, methanol-d4) δ (ppm): 1.89 (3H, s), 2.50 (3H, s), 3.11 (4H, br dd), 3.49 (1H, dd, J=13.7 and 7.9 Hz), 3.60 (1H, dd, J=13.7 and 4.1 Hz), 3.86 (4H, br dd), 4.15 (2H, d, JAB=18.1 Hz), 4.92 (1H, dd, J=7.0 and 4.3 Hz), 6.76 (1H, br s), 6.94 (1H, br s), 7.27–7.39 (3H, m), 7.50 (1H, s).

Workup

  1. temperatureThe reaction was cooled down to RT
  2. extractionThe aqueous phase was extracted with dichloromethane (5×)
  3. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue (0.012 g) was dissolved in dichloromethane (1.5 mL)
  7. additiontreated with SCX resin (0.750 g)
  8. washthe resin was washed with dichloromethane
  9. customThe ammonia solution was evaporated

Sources & evidence

ORD record
ord-16a292b380cd4d7cb71f427a69aa8ddc
Source dataset
uspto-grants-2007_05
Patent number
US07223757B2

Reaction notes

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