4-Methylmorpholine → 6-Nitro-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one

HRID 1040688Notes

Reaction equation

[NH2:1][CH2:2][CH2:3][NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[C:6]=1[C:7](O)=[O:8].C1C=CC2N(O)N=NC=2C=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[N+:14]([C:10]1[C:6]2[C:7](=[O:8])[NH:1][CH2:2][CH2:3][NH:4][C:5]=2[CH:13]=[CH:12][CH:11]=1)([O-:16])=[O:15]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of 2-(2-amino-ethylamino)-6-nitro-benzoic acid (0.35 g, 0.0013 mol) in DMF (10 mL) was added HOBt (0.22 g, 0.0016 mol), BOP (0.71 g, 0.0016 mol) and N-methylmorpholine (0.18 mL, 0.0016 mol) at 0° C. under nitrogen. The reaction was stirred for at 0° C. for 1 h then warmed to room temperature overnight. The reaction was diluted with ethyl acetate (20 mL) and washed with water, 10% aqueous HCl, water and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The product was purified by ISCO purification using 5-15% methanol-methylene chloride to give desired 6-Nitro-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (0.22 g, 82% yield). 1H NMR (400 MHz, CDCl3) δ 9.9 (s, 1H), 7.41 (t, 1H, J=7.6 Hz), 7.12 (d, 1H, J=7.6 Hz), 6.95 (d, 1H, J=7.6 Hz), 3.92 (broad s, 1H), 3.25 (m, 2H), 2.73 (m, 2H); MS (m/e) 208 (M+1).

Workup

temperaturethen warmed to room temperature overnight
washwashed with water, 10% aqueous HCl, water and brine
dry with materialThe organic phase was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe product was purified by ISCO purification

Sources & evidence

ORD record: ord-42526b2f401343f6b2fe3700c2813070
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552186B2

Reaction notes

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