Nitrogen → (3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrile

HRID 1941764Notes

Reaction equation

HRID 1941764 reaction equation
[NH2:1][C:2]1[C:11]([F:12])=[C:10]([F:13])[C:9]2[O:14][CH2:15][C@H:16]([CH3:17])[N:7]3[C:8]=2[C:3]=1[C:4](=[O:21])[C:5]([C:18]([NH2:20])=O)=[CH:6]3.C(N(CC)CC)C.O=P(Cl)(Cl)Cl.N#N>C(Cl)Cl>[NH2:1][C:2]1[C:11]([F:12])=[C:10]([F:13])[C:9]2[O:14][CH2:15][C@H:16]([CH3:17])[N:7]3[C:8]=2[C:3]=1[C:4](=[O:21])[C:5]([C:18]#[N:20])=[CH:6]3

Participants

6

Reactant 4

HCID 947NitrogenHCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 58346341HCID 58346341, compound

Product 1

HCID 58346338(3S)-8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carbonitrileYield 82.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4 (500 mg, 1.69 mmol) and triethylamine (1.2 mL, 8.5 mmol.) in DCM (20 mL) was added POCl3 (431 μL, 3.2 mmol.) dropwise under Ar (or N2) at 0° C. Stirring was continued for an additional 5 h. A dark colored mixture was formed. Upon completion of the reaction, DCM was removed under vacuo and the residue was washed several times with water. The solid was dried under vacuum to give 5 (385 mg, 82% yield). This product was not very soluble except in DMF or DMSO and was used in the next step without further purification.

Workup

  1. customA dark colored mixture was formed
  2. customwas removed under vacuo
  3. washthe residue was washed several times with water
  4. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-efcd0ffb15e14b71bd9e83ceb76253ee
Source dataset
uspto-grants-2013_03
Patent number
US08389514B2

Reaction notes

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