Water → HCID 58204706, compound

HRID 1498557Notes

Reaction equation

[F:1][C:2]([F:27])([F:26])[CH2:3][N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20](C(O)=O)=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:25]=2)=[N:7][CH:6]=[N:5]1.C([N:30](CC)CC)C.C1C=CC(OP(OC2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1.O>CN(C=O)C.C(OCC)(=O)C.C([O-])(O)=O.[Na+]>[F:26][C:2]([F:27])([F:1])[CH2:3][N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([NH2:30])=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:25]=2)=[N:7][CH:6]=[N:5]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-9-carboxylic acid (170 mg, 0.45 mmol) and triethylamine (95 uL, 0.68 mmol), in DMF (3.5 mL), was added diphenylphosphonic azide (146 uL, 0.68 mmol) at ambient temperature. After 3 h, water (0.45 mL) was added and the reaction mixture was heated at 100° C. After 1 h, the mixture was diluted with ethyl acetate and sat. NaHCO3. The aqueous layer was extracted into ethyl acetate (3×), and the combined organics were filtered through a plug of celite and concentrated in vacuo. The crude residue was purified by preparative HPLC to afford 493 as a white solid (85 mg, 54%). LC/MS (ESI+): m/z 351 (M+H). 1H NMR (400 MHz, DMSO) δ 8.05 (s, 1H), 8.01 (d, J=8.7 Hz, 1H), 7.89 (s, 1H), 6.38 (dd, J=8.7, 2.2 Hz, 1H), 6.18 (d, J=2.2 Hz, 1H), 5.92 (q, J=8.9 Hz, 2H), 5.56 (s, 2H), 4.41 (dd, J=12.3, 5.6 Hz, 4H)

Workup

waitAfter 1 h
extractionThe aqueous layer was extracted into ethyl acetate (3×)
filtrationthe combined organics were filtered through a plug of celite and
concentrationconcentrated in vacuo
customThe crude residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-2b8d3f68990248178a79cac3dfe2319b
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09198918B2

Reaction notes

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