Water → N-(5-benzyl-1,2-oxazol-3-yl)-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide

HRID 1748349Notes

Reaction equation

[O:1]=[C:2]1[C:8]2=[CH:9][C:10]3[CH:11]=[CH:12][C:13]([C:16]([OH:18])=O)=[CH:14][C:15]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1.[CH2:19]([C:26]1[O:30][N:29]=[C:28]([NH2:31])[CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.P(Cl)(Cl)(Cl)=O.O>N1C=CC=CC=1>[CH2:19]([C:26]1[O:30][N:29]=[C:28]([NH:31][C:16]([C:13]2[CH:12]=[CH:11][C:10]3[CH:9]=[C:8]4[C:2](=[O:1])[NH:3][CH2:4][CH2:5][CH2:6][N:7]4[C:15]=3[CH:14]=2)=[O:18])[CH:27]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A 0.5-2 mL microwave reactor vial is charged with a mixture of 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylic acid (Intermediate J, 100 mg, 0.41 mmol) and 5-benzyl-3-aminoisoxazole (107 mg, 0.61 mmol) in pyridine (500 μL) and the vial is sealed with a Teflon lined septa cap. The mixture is cooled to 0° C. and phosphorous oxychloride (40 μL, 0.43 mmol) is added. The mixture is allowed to warm to room temperature and is then irradiated in a microwave reactor at 150° C. for 60 min. The mixture is poured into water and the resulting solid is collected by filtration and is purified via preparative HPLC using a gradient elution from 10-75% acetonitrile/water with 0.1% TFA to obtain the title compound (87 mg, 53%). LCMS: 401.20 (M+H+). (System V1)

Workup

temperatureto warm to room temperature
customis then irradiated in a microwave reactor at 150° C. for 60 min
filtrationthe resulting solid is collected by filtration
customis purified via preparative HPLC
washa gradient elution from 10-75% acetonitrile/water with 0.1% TFA

Sources & evidence

ORD record: ord-a5662534b3c94f0eb279984f1bf8c9fc
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150577B2

Reaction notes

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