Methanol → 3-((8-(3-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid

HRID 1751009Notes

Reaction equation

HRID 1751009 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([CH2:11][CH2:12][CH2:13][N:14]2[CH2:41][CH2:40][C:17]3([N:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:20][N:19]([CH2:28][C:29]4[CH:30]=[C:31]([CH:36]=[CH:37][CH:38]=4)[C:32]([O:34]C)=[O:33])[C:18]3=[O:39])[CH2:16][CH2:15]2)[C:3]1=[O:42].[OH-].[Li+].CO>O>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([CH2:11][CH2:12][CH2:13][N:14]2[CH2:15][CH2:16][C:17]3([N:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:20][N:19]([CH2:28][C:29]4[CH:30]=[C:31]([CH:36]=[CH:37][CH:38]=4)[C:32]([OH:34])=[O:33])[C:18]3=[O:39])[CH2:40][CH2:41]2)[C:3]1=[O:42]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 66652256methyl 3-((8-(3-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 580467563-((8-(3-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acidYield 17.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
35 °C

Procedure

A solution of methyl 3-((8-(3-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (326 mg, 0.575 mmol, 1 equiv) and lithium hydroxide (48.3 mg, 1.15 mmol, 2.0 equiv) in a 4:1 mixture of methanol and water (5 ml t/v) was stirred at 35° C. for 24 hrs. The reaction was concentrated in vacuo and purified using preparatory high performance liquid chromatography. The combined pure fractions were lyophilized to afford the acetate salt of the title compound as a white solid (56 mg, 17%); 1H NMR (400 MHz, DMSO-d6): δ 1.61 (d, 2H, J=13.6 Hz), 1.84 (t, 2H, J=6.8 Hz); 2.37 (t, 2H, J=7.2 Hz, J=6.4 Hz); 2.54-2.59 (m, 2H); 2.66-2.73 (m, 4H); 3.32 (s, 3H); 3.91 (t, 2H, J=6.8 Hz); 4.58 (s, 2H); 4.60 (s, 2H); 6.76 (t, 1H, J=7.2 Hz); 6.85 (d, 2H, J=8 Hz); 7-7.07 (m, 2H); 7.12-7.15 (m, 1H); 7.2-7.26 (m, 3H); 7.47-7.53 (m, 2H); 7.86-7.88 (m, 2H); 12.9 (bs, 1H); MS for C32H35N5O4 m/z 554.05 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompurified

Sources & evidence

ORD record
ord-9407bbff0feb4daba18a06f37c773dc7
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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