Triethylamine → 8'-amino-9'-fluoro-7'-oxo-10'-[3-(2-pyridyl)propylamino]spiro[oxolane-3,3'(2'H)-[7H]pyrido[1,2,3-de][1,4]benzoxazine]-6'-carboxylic acid

HRID 444792Notes

Reaction equation

HRID 444792 reaction equation
[NH2:1][C:2]1[C:18]2[C:17](=[O:19])[C:16]([C:20]([OH:22])=[O:21])=[CH:15][N:7]3[C:8]4([CH2:14][CH2:13][O:12][CH2:11]4)[CH2:9][O:10][C:5]([C:6]=23)=[C:4](F)[C:3]=1[F:24].[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][CH2:32][CH2:33][NH2:34].C(N(CC)CC)C.[NH4+].[Cl-]>CS(C)=O.O>[NH2:1][C:2]1[C:18]2[C:17](=[O:19])[C:16]([C:20]([OH:22])=[O:21])=[CH:15][N:7]3[C:8]4([CH2:14][CH2:13][O:12][CH2:11]4)[CH2:9][O:10][C:5]([C:6]=23)=[C:4]([NH:34][CH2:33][CH2:32][CH2:31][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=2)[C:3]=1[F:24]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 31596143-(Pyridin-2-yl)propan-1-amineHCID 58134865HCID 58134865, compound

Product 1

HCID 252539818'-amino-9'-fluoro-7'-oxo-10'-[3-(2-pyridyl)propylamino]spiro[oxolane-3,3'(2'H)-[7H]pyrido[1,2,3-de][1,4]benzoxazine]-6'-carboxylic acidYield 93%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A solution of 8′-amino-9′,10′-difluoro-7′-oxospiro[oxolane-3,3′(2′H)-[7H]pyrido[1,2,3-de][1,4]benzoxazine]-6′-carboxylic acid (300 mg, 0.887 mmol), 3-(2-pyridyl)propylamine (181 mg, 1.33 mmol) and triethylamine (0.185 mL, 1.33 mmol) in DMSO (4 mL) was stirred at 100° C. for 6 h. To the reaction mixture, water and saturated NH4Cl solution were added to pH<4 and stirred for 30 min. The resulting precipitate was collected by filtration, washed with water and EtOH, and dried to yield 8′-amino-9′-fluoro-7′-oxo-10′-[3-(2-pyridyl)propylamino]spiro[oxolane-3,3′(2′H)-[7H ]pyrido[1,2,3-de][1,4]benzoxazine]-6′-carboxylic acid (373 mg, 93%) as a pale yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 1.90-1.98 (2H, m), 2.26-2.39 (2H, m), 2.77 (2H, t, J=7.3 Hz), 3.42-3.51 (2H, m), 3.73 (1H, d, J=10.4 Hz), 3.91-3.97 (1H, m), 4.07-4.13 (1H, m), 4.16 (1H, d, J=10.4 Hz), 4.24 (1H, d, J=11.0 Hz), 4.35 (1H, d, J=11.0 Hz), 6.01-6.10 (1H, m), 6.92 (2H, brs), 7.18 (1H, dd, J=6.7, 5.5 Hz), 7.24 (1H, d, J=7.9 Hz), 7.67 (1H, td, J=7.3, 1.8 Hz), 8.42 (1H, s), 8.45 (1H, d, J=4.3 Hz), 15.27 (1H, s). HRESIMS (+) 455.17350 (Calcd for C23H23FN4O5, 455.17307).

Workup

  1. filtrationThe resulting precipitate was collected by filtration
  2. washwashed with water and EtOH
  3. customdried

Sources & evidence

ORD record
ord-afc0865e2ea546e9b67b3ff0a608596a
Source dataset
uspto-grants-2013_07
Patent number
US08476261B2

Reaction notes

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