Lithium Hydroxide → HCID 9935615, compound

HRID 1601054Notes

Reaction equation

HRID 1601054 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][NH:11][C:12]([C:14]1[CH:15]=[CH:16][C:17]2[NH:23][CH:22]([CH2:24][C:25]([O:27]C)=[O:26])[C:21](=[O:29])[N:20]([CH2:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:19][C:18]=2[CH:38]=1)=[O:13].[Li+].[OH-].C1COCC1.C(O)(C(F)(F)F)=O>O>[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][NH:11][C:12]([C:14]1[CH:15]=[CH:16][C:17]2[NH:23][CH:22]([CH2:24][C:25]([OH:27])=[O:26])[C:21](=[O:29])[N:20]([CH2:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:19][C:18]=2[CH:38]=1)=[O:13]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 53964968HCID 53964968, compound

Product 1

HCID 9935615HCID 9935615, compoundYield 85.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
42.5 °C

Procedure

A mixture of methyl (±)-7-[[[(2-benzimidazolyl)methyl]amino]carbonyl]-3-oxo-4-(2-phenylethyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetate (413.1 mg, 0.81 mmol), 1.0 N LiOH (0.97 mL, 0.97 mmol), THF (4 mL), and H2O (3 mL) was stirred at 40-45° C. for 20 min, and the resulting solution was stirred at RT for 17 h. Acidification with TFA (0.19 mL, 2.4 mmol) and concentration left an off-white solid. Recrystallization from CH3CN/H2O gave the title compound (343.2 mg, 69%) as a colorless powder: HPLC (PRP-1®, 30% CH3CN/H2O-0.1% TFA) K'=1.5; 1H NMR (400 MHz, CD3OD) δ 7.68-7.75 (m, 2H), 7.60 (dd, J=8.6, 2.2 Hz, 1H), 7.51-7.58 (m, 2H), 7.49 (d, J=2.2 Hz, 1H), 7.07-7.22 (m, 5H), 6.61 (d, J=8.6 Hz, 1H), 5.46 (d, J=16.8 Hz, 1H), 5.18 (dd, J=9.0, 5.1 Hz, 1H), 4.95 (s, 2H), 3.81 (d, J=16.8 Hz, 1H), 3.61-3.78 (m, 2H), 2.94 (dd, J=16.8, 9.0 Hz, 1H), 2.71-2.83 (m, 2H), 2.65 (dd, J=16.8, 5.1 Hz, 1H); MS (ES) m/e 498.4 (M+H)+. Anal. Calcd for C28H27N5O4.CF3CO2H.0.25 H2O: C, 58.49; H, 4.66; N, 11.37. Found: C, 58.52; H, 4.47; N, 11.04.

Workup

  1. stirringthe resulting solution was stirred at RT for 17 h
  2. waitleft an off-white solid
  3. customRecrystallization from CH3CN/H2O

Sources & evidence

ORD record
ord-cc19e24937e84f96ae95c80f6772b856
Source dataset
uspto-grants-1999_11
Patent number
US05977101

Reaction notes

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