Triethylamine → (3R)-8-amino-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-10-[2-(2-pyridylamino)ethylamino]-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid

HRID 561178Notes

Reaction equation

HRID 561178 reaction equation
[NH2:1][C:2]1[C:16]2[C:15](=[O:17])[C:14]([C:18]([OH:20])=[O:19])=[CH:13][N:7]3[C@@H:8]([CH2:11][F:12])[CH2:9][O:10][C:5]([C:6]=23)=[C:4](F)[C:3]=1[F:22].[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[NH:29][CH2:30][CH2:31][NH2:32].C(N(CC)CC)C>CS(C)=O>[NH2:1][C:2]1[C:16]2[C:15](=[O:17])[C:14]([C:18]([OH:20])=[O:19])=[CH:13][N:7]3[C@@H:8]([CH2:11][F:12])[CH2:9][O:10][C:5]([C:6]=23)=[C:4]([NH:32][CH2:31][CH2:30][NH:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)[C:3]=1[F:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 410428N~1~-(Pyridin-2-yl)ethane-1,2-diamineHCID 66999235(3R)-8-amino-9,10-difluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid

Product 1

HCID 59003011(3R)-8-amino-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-10-[2-(2-pyridylamino)ethylamino]-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acidYield 67.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (3R)-8-amino-9,10-difluoro-3-fluoromethyl-2,3-dihydro-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (200 mg, 0.636 mmol), 2-(2-pyridylamino)ethylamine (131 mg, 0.955 mmol), and triethylamine (0.13 mL, 0.933 mmol) in DMSO (2.0 mL) was stirred at 120° C. for 2.5 h. After dilution of the reaction mixture with 10% MeOH in CHCl3, the whole mixture washed with water and the washing was extracted with 10% MeOH in CHCl3 three times. The combined the organic layer and the extracts washed with water, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Flash chromatography of the residue (10% MeOH in CHCl3) gave (3R)-8-amino-9-fluoro-3-fluoromethyl-2,3-dihydro-7-oxo-10-[2-(2-pyridylamino)ethylamino]-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (184 mg, 67%) as a yellow powder.

Workup

  1. washAfter dilution of the reaction mixture with 10% MeOH in CHCl3, the whole mixture washed with water
  2. extractionthe washing was extracted with 10% MeOH in CHCl3 three times
  3. washthe extracts washed with water
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2ea12d3c4bd4483eac62d35217164c12
Source dataset
uspto-grants-2011_11
Patent number
US08063221B2

Reaction notes

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