Trifluoroacetic acid → HCID 69522037, compound

HRID 459902Notes

Reaction equation

HRID 459902 reaction equation
C(OC([N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:11][C@@H:10]([NH2:25])[C:9]1=[O:26])=O)(C)(C)C.[H-].[Na+].Br[CH2:30][CH2:31][CH2:32][CH2:33][N:34]1[C:38](=[O:39])[C:37]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:36]2[C:35]1=[O:44].FC(F)(F)[C:47](O)=[O:48].C(N(CC)CC)C.Cl.[NH:60]1[CH2:65][CH2:64][CH:63]([N:66]2[CH2:75][C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[NH:68][C:67]2=[O:76])[CH2:62][CH2:61]1>CN(C)C=O.C(Cl)Cl.O1CCCC1.C(N(CC)CC)C.O>[O:44]=[C:35]1[C:36]2[C:37](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38](=[O:39])[N:34]1[CH2:33][CH2:32][CH2:31][CH2:30][N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C:12]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:11][C@@H:10]([NH:25][C:47]([N:60]2[CH2:61][CH2:62][CH:63]([N:66]3[CH2:75][C:74]4[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=4)[NH:68][C:67]3=[O:76])[CH2:64][CH2:65]2)=[O:48])[C:9]1=[O:26]

Participants

12

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 93575N-(4-Bromobutyl)phthalimideHCID 183213553-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one hydrochlorideHCID 69522106HCID 69522106, compound

Product 1

HCID 69522037HCID 69522037, compound

Reagents, catalysts & solvents 5

HCID 8471TriethylamineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-t-butyloxycarbonyl-(3R)-3-amino-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine (40.0 mg, 0.114 nmol) in dimethylformamide (1.5 mL) was stirred with sodium hydride (6.83 mg, 0.17 mmol, 60% dispersion in oil) for 15 min, then N-(4-bromobutyl)-phthalimide (32.1 mg, 0.114 mmol) was added. The reaction was stirred overnight and worked up with methylene chloride and water. The crude product was dissolved in methylene chloride (4.5 mL) containing trifluoroacetic acid (1.5 mL) and stirred for 1 h. The solvents were removed in vacuo, and the crude product dissolved in tetrahydrofuran (1 mL) along with p-nitrochloroformate (14.5 mg, 0.072 mmol) and triethylamine (0.20 mL, 0.14 mmol). After stirring for 2 h, 3-(4-piperidinyl)-3,4-dihydroquinazolin-2(1H)-one hydrochloride (19.3 mg, 0.072 mmol) and triethylamine (0.020 mL, 0.14 nmol) was added and the reaction stirred overnight. The crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution), to yield the title compound (19 mg). MS 710.3123 (M+1)

Workup

  1. stirringstirred for 1 h
  2. customThe solvents were removed in vacuo
  3. stirringAfter stirring for 2 h
  4. stirringthe reaction stirred overnight
  5. customThe crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution)

Sources & evidence

ORD record
ord-137753867fce4804bec2d4022a834e08
Source dataset
uspto-grants-2007_03
Patent number
US07196079B2

Reaction notes

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