Phenylacetylene → 7,8-Dimethoxy-1-methyl-5-(2-phenylethynyl)-1,3-dihydro-1,4-benzodiazepin-2-one

HRID 1297099Notes

Reaction equation

Cl[C:2]1[C:8]2[CH:9]=[C:10]([O:15][CH3:16])[C:11]([O:13][CH3:14])=[CH:12][C:7]=2[N:6]([CH3:17])[C:5](=[O:18])[CH2:4][N:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:38]1([C:44]#[CH:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CC#N.Cl[Pd]Cl.[Cu]I>[CH3:16][O:15][C:10]1[C:11]([O:13][CH3:14])=[CH:12][C:7]2[N:6]([CH3:17])[C:5](=[O:18])[CH2:4][N:3]=[C:2]([C:45]#[C:44][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:8]=2[CH:9]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 240 mg (0.89 mmol) of 5-chloro-7,8-dimethoxy-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one XVIIIaa in 7 ml of CH3CN, add under an inert atmosphere 17 mg (0.1 mmol) of PdCl2, 30 mg (0.16 mmol) of CuI. Stir for 5 minutes, then add 68 mg (0.23 mmol) of PPh3, 185 μl of Net3 and 150 μl of phenylacetylene. Heat the mixture at 55° C. for 3 hours. Evaporate to dryness and purify by silica chromatography (AcOEt 1/hexane 1, then AcOEt). Recrystallize in EtOH. Yield: 45%. 1H-NMR (DMSO, 200 MHz): d 3.33 (s, 3H, NCH3), 3.70–3.91 (m, 7H, 1HCH2+20CH3), 4.50–5.60 (m, 1HCH2), 7.06 (s, 1H Ar), 7.32 (s, 1H Ar), 7.48–7.68 (m, 5H Ar). Mass: (M+H)+=335.16.

Workup

customEvaporate to dryness
custompurify by silica chromatography (AcOEt 1/hexane 1
customRecrystallize in EtOH

Sources & evidence

ORD record: ord-a37efcbce1fc4a2897503a7a8aa0c36d
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07250410B2

Reaction notes

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