4-Methylmorpholine → HCID 57612764, compound

HRID 1668416Notes

Reaction equation

[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C@H:12]([C:18](=[O:36])[N:19]1[C@H:24]([C:25](=[O:35])[NH:26][CH2:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:23][CH2:22][CH2:21][NH:20]1)[CH2:13][CH2:14][C:15](O)=[O:16].CN1CCOCC1.P(Cl)(Cl)(Cl)(Cl)Cl>C1COCC1>[CH2:27]([NH:26][C:25]([C@H:24]1[N:19]2[C:18](=[O:36])[C@@H:12]([N:3]3[C:4](=[O:11])[C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[C:2]3=[O:1])[CH2:13][CH2:14][C:15](=[O:16])[N:20]2[CH2:21][CH2:22][CH2:23]1)=[O:35])[CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (S)-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-5-oxo-5-((S)-6-phenethylcarbamoyl-tetrahydro-pyridazin-1-yl)-pentanoic acid (0.74 g, 1.5 mmol) and N-methylmorpholine (0.6 g, 6.0 mmol) in THF (20 mL) at 0° C., is added PCl5 (470 mg, 2.25 mmol) in one portion. After stirring at 0° C. for 3 hours, the reaction mixture is concentrated and purified by chromatography (CH2Cl2/MeOH:97/3) to yield (1S,9S)-9-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid phenethyl-amide (310 mg, 43.6%) as white solid. (NMR and MS data confirmed, U-3133-65).

Workup

concentrationthe reaction mixture is concentrated
custompurified by chromatography (CH2Cl2/MeOH:97/3)

Sources & evidence

ORD record: ord-10bc2a13a40d4485a9dc4b5f9bf678aa
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989441B2

Reaction notes

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