Diisopropylethylamine → HCID 178512337, compound

HRID 1867631Notes

Reaction equation

HRID 1867631 reaction equation
C([N:4](C(C)C)CC)(C)C.O=C1NC(C2C=CC=C(OC)C=2)=CN1C1CCN(C(O[C@H:33]2[N:39]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:37]3[CH:46]=[CH:47][CH:48]=[CH:49][C:36]=3[N:35]([CH2:50][C:51]([F:54])([F:53])[F:52])[C:34]2=[O:55])=O)CC1.C1C=CC(O[C:63](OC2C=CC=CC=2)=[N:64][C:65]#[N:66])=CC=1.Cl.[C:75]1([C:81]2[NH:82][C:83](=[O:92])[N:84]([CH:86]3[CH2:91][CH2:90][NH:89][CH2:88][CH2:87]3)[CH:85]=2)[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1>C(Cl)Cl.C(O)CCCC>[C:63]([N:64]=[C:65]([N:89]1[CH2:88][CH2:87][CH:86]([N:84]2[CH:85]=[C:81]([C:75]3[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=3)[NH:82][C:83]2=[O:92])[CH2:91][CH2:90]1)[NH:66][C@@H:33]1[N:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:37]2[CH:46]=[CH:47][CH:48]=[CH:49][C:36]=2[N:35]([CH2:50][C:51]([F:53])([F:54])[F:52])[C:34]1=[O:55])#[N:4]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 688090Diphenyl N-CyanocarbonimidateHCID 67344326HCID 67344326, compound2×HCID 68566597HCID 68566597, compound

Product 1

HCID 178512337HCID 178512337, compound

Reagents, catalysts & solvents 2

HCID 62761-PentanolSolventHCID 6344DichloromethaneSolvent

Procedure

Diisopropylethylamine (107 uL, 0.615 mmol) was added to a solution of (3R) 3-amino-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine (205 mg, 0.615 mmol) and diphenyl N-cyanocarbonimidate (147 mg, 0.615 mmol) in methylene chloride (5 mL). The reaction was stirred at room temperature for 72 h, then quenched with 0.5 N sodium hydroxide. The methylene chloride was washed with water and saturated brine, and dried over sodium sulfate. The solid product (139 mg, 0.291 mmol) was dissolved in 1-pentanol (2 mL) along with 4-phenyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazol-2-one hydrochloride (81.4 mg, 0.291 mmol) and diisopropylethylamine (76.1 uL, 0.437 mmol), and refluxed under argon overnight. An additional equivalent of 4-phenyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazol-2-one hydrochloride was added and the reaction refluxed overnight. The reaction was concentrated and purified by chromatography (silica gel, 0-5% methanol in methylene chloride containing 0.1% ammonium hydroxide, gradient elution), providing the title compound. MS 627.2464 (M+1)

Workup

  1. customquenched with 0.5 N sodium hydroxide
  2. washThe methylene chloride was washed with water and saturated brine
  3. dry with materialdried over sodium sulfate
  4. temperaturerefluxed under argon overnight
  5. temperaturethe reaction refluxed overnight
  6. concentrationThe reaction was concentrated
  7. custompurified by chromatography (silica gel, 0-5% methanol in methylene chloride containing 0.1% ammonium hydroxide, gradient elution)

Sources & evidence

ORD record
ord-0c56363a972b4102be5eaced2e93fcfc
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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