Triethylamine → HCID 11455453, compound

HRID 459899Notes

Reaction equation

HRID 459899 reaction equation
[C:1]([OH:6])(=O)C(O)=O.[NH2:7][C@@H:8]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:12]2[CH:21]=[CH:22][CH:23]=[CH:24][C:11]=2[N:10]([CH2:25][CH3:26])[C:9]1=[O:27].C(N(CC)CC)C.Cl.[NH:36]1[CH2:41][CH2:40][CH:39]([N:42]2[CH2:51][C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[NH:44][C:43]2=[O:52])[CH2:38][CH2:37]1>O1CCCC1.CS(C)=O>[O:52]=[C:43]1[N:42]([CH:39]2[CH2:40][CH2:41][N:36]([C:1]([NH:7][C@@H:8]3[N:14]=[C:13]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:12]4[CH:21]=[CH:22][CH:23]=[CH:24][C:11]=4[N:10]([CH2:25][CH3:26])[C:9]3=[O:27])=[O:6])[CH2:37][CH2:38]2)[CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[NH:44]1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 183213553-(Piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one hydrochlorideHCID 69522931HCID 69522931, compound

Product 1

HCID 11455453HCID 11455453, compoundYield 24.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (3R)-3-amino-1-ethyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine oxalic acid salt (27.6 mg, 0.0747 mmol) and p-nitrophenylchloroformate (15.1 mg, 0.0747 mmol) was dissolved in tetrahydrofuran (0.5 mL), and cooled to 0° C. under argon. Triethylamine (10.4 uL, 0.0747 mmol) was added and the reaction stirred for 1 h. Additional triethylamine (26.0 uL, 0.186 mmol) was added, along with 3-(4-piperidinyl)-3,4 dihydroquinazolin-2(1H)-one hydrochloride (20.0 mg, 0.0747 mmol) in dimethylsulfoxide (0.5 mL). The reaction was allowed to warm to room temperature and 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), isolating 4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)-N-[(3R)-1-ethyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]piperidine-1-carboxamide (10.0 mg) MS 537 (M+1) and 4-(2-oxo-1,4-dihydro-4-hydroxyquinazolin-3(2H)-yl)-N-[(3R)-1-ethyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]piperidine-1-carboxamide (5 mg) MS 535 (M−17).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. 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-4f8dd03cbec4414197343ace7294dd19
Source dataset
uspto-grants-2007_03
Patent number
US07196079B2

Reaction notes

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