Lithium Hydroxide → HCID 21830368, compound

HRID 1601056Notes

Reaction equation

HRID 1601056 reaction equation
[CH:1]([N:4]1[CH2:10][C:9]2[CH:11]=[C:12]([C:15]([NH:17][CH2:18][C:19]3[NH:20][C:21]4[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=4[N:23]=3)=[O:16])[CH:13]=[CH:14][C:8]=2[NH:7][CH:6]([CH2:28][C:29]([O:31]C)=[O:30])[C:5]1=[O:33])([CH3:3])[CH3:2].[Li+].[OH-].C1COCC1.CC#N.O>O>[CH:1]([N:4]1[CH2:10][C:9]2[CH:11]=[C:12]([C:15]([NH:17][CH2:18][C:19]3[NH:23][C:22]4[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=4[N:20]=3)=[O:16])[CH:13]=[CH:14][C:8]=2[NH:7][CH:6]([CH2:28][C:29]([OH:31])=[O:30])[C:5]1=[O:33])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 18373917Acetonitrile--water (1/1)HCID 54218403HCID 54218403, compound

Product 1

HCID 21830368HCID 21830368, compoundYield 110.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
35 °C

Procedure

A mixture of methyl (±)-4-isopropyl-7-[[[(2-benzimidazolyl)methyl]amino]carbonyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetate (275.1 mg, 0.61 mmol), 1.0 N LiOH (0.73 mL, 0.73 mmol), THF (3 mL), and H2O (2.3 mL) was stirred at 35° C. for 45 min, and the resulting solution was stirred at RT. After 17.5 h, the solution was filtered, and the filtrate was neutralized with 1.0 N HCl (0.73 mL). Since the product did not precipitate, the solution was acidified with TFA (0.2 mL) and concentrated. The resulting solid was triturated with H2O to leave a nearly colorless solid, which was dissolved with warming in 1:1 CH3CN/H2O. The solution was cooled to RT and diluted with several volumes of H2O/0.1% TFA. ODS chromatography (20% CH3CN/H2O-0.1% TFA), concentration, and lyophilization gave the title compound (293.4 mg, 80%) as a colorless powder: HPLC (PRP-1®, 20% CH3CN/H2O-0.1% TFA) K'=2.5; 1H NMR (400 MHz, CD3OD) δ 7.70-7.76 (m, 2H), 7.65 (d, J=2.2 Hz, 1H), 7.61 (dd, J=8.5, 2.2 Hz, 1H), 7.53-7.60 (m, 2H), 6.62 (d, J=8.5 Hz, 1H), 5.33 (d, J=16.9 Hz, 1H), 5.21 (dd, J=8.9, 5.2 Hz, 1H), 4.97 (d, J=1.9 Hz, 2H), 4.72-4.85 (m, 1H), 4.10 (d, J=16.9 Hz, 1H), 2.96 (dd, J=16.8, 8.9 Hz, 1H), 2.65 (dd, J=16.8, 5.2 Hz, 1H), 1.21 (d, J=6.7 Hz, 3H), 1.03 (d, J=6.8 Hz, 3H); MS (ES) m/e 436.2 (M+H)+. Anal. Calcd for C23H25N5O4.1.25 CF3CO2H.1.25 H2O: C, 51.00; H, 4.83; N, 11.66. Found: C, 51.12; H, 4.91; N, 11.37.

Workup

  1. stirringthe resulting solution was stirred at RT
  2. waitAfter 17.5 h
  3. filtrationthe solution was filtered
  4. concentrationconcentrated
  5. customThe resulting solid was triturated with H2O
  6. customto leave a nearly colorless solid, which
  7. dissolutionwas dissolved
  8. temperatureThe solution was cooled to RT
  9. concentrationODS chromatography (20% CH3CN/H2O-0.1% TFA), concentration, and lyophilization

Sources & evidence

ORD record
ord-2c9367ffc04f42e38251eb7fa6fbfa19
Source dataset
uspto-grants-1999_11
Patent number
US05977101

Reaction notes

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