Diisopropylethylamine → HCID 58728735, compound

HRID 1992129Notes

Reaction equation

HRID 1992129 reaction equation
[O:1]1[CH2:5][CH2:4][C@H:3]([O:6][C:7]([O:9]N2C(=O)CCC2=O)=O)[CH2:2]1.Cl.Cl.[CH3:19][C:20]1[N:24]([CH:25]2[CH2:31][CH:30]3[N:32]([CH2:33][CH2:34][C:35]4([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]4)[CH:27]([CH2:28][CH2:29]3)[CH2:26]2)[C:23]2[CH:47]=[CH:48][CH:49]=[CH:50][C:22]=2[N:21]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[CH3:19][C:20]1[N:24]([CH:25]2[CH2:31][C@H:30]3[N:32]([CH2:33][CH2:34][C:35]4([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[CH2:36][CH2:37][N:38]([C:7]([O:6][C@H:3]5[CH2:4][CH2:5][O:1][CH2:2]5)=[O:9])[CH2:39][CH2:40]4)[C@H:27]([CH2:28][CH2:29]3)[CH2:26]2)[C:23]2[CH:47]=[CH:48][CH:49]=[CH:50][C:22]=2[N:21]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11229944Carbonic Acid 2,5-Dioxopyrrolidin-1-yl (S)-Tetrahydrofuran-3-yl EsterHCID 686757782-methyl-1-{8-[2-(4-phenyl piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride

Product 1

HCID 58728735HCID 58728735, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-({[(3S)-tetrahydrofuran-3-yloxy]carbonyl}oxy)pyrrolidine-2,5-dione (U.S. Pat. No. 6,344,465) (55 mg, 0.24 mmol), amine dihydrochloride II (100 mg, 0.199 mmol) and N,N-diisopropylethylamine (0.14 mL, 0.80 mmol) in acetonitrile (3 mL) was stirred overnight at rt. The solvent was removed at reduced pressure and the remaining material was dissolved in dichloromethane, washed with saturated sodium bicarbonate solution and dried over magnesium sulfate. Filtration and evaporation of the dichloromethane solution provided the crude product which was purified by chromatography on silica gel eluting with 5% methanol/dichloromethane. Title compound in example 692 was obtained as a white hygroscopic powder (70 mg, 65%). 1H NMR (400 MHz, CDCl3) δ 7.66 (d, 1H, J=8 Hz), 7.37 (m, 2H), 7.30-7.20 (m, 4H), 7.16 (m, 2H), 5.25 (m, 1H), 4.61 (m, 1H), 3.85 (m, 4H), 3.73 (m, 2H), 3.22 (m, 4H), 2.58 (br s, 3H), 2.36 (m, 2H), 2.17 (m, 3H), 2.05-1.70 (m, 13H). HRMS C33H42N4O3 m/z 543.3335 (M+H)Cal., 543.3331 (M+H)Obs..

Workup

  1. customThe solvent was removed at reduced pressure
  2. dissolutionthe remaining material was dissolved in dichloromethane
  3. washwashed with saturated sodium bicarbonate solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationFiltration and evaporation of the dichloromethane solution
  6. customprovided the crude product which
  7. customwas purified by chromatography on silica gel eluting with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-a3c09dc320594e599710cd75fe6a6257
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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