Triethylamine → 2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxamide

HRID 1776860Notes

Reaction equation

HRID 1776860 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19](O)=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:22]=1.[NH4+].[Cl-].C1C=CC2N(O)N=[N:31]C=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19]([NH2:31])=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:22]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 867282632-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylic acid

Product 1

HCID 867282642-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxamideYield 33.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylic acid (60 mg, 0.19 mmol), NH4Cl (20 mg, 0.38 mmol), HOBT (38 mg, 0.28 mmol), EDCI (54 mg, 0.28 mmol) and triethylamine (76 mg, 0.75 mmol) in DMF (1 mL) was stirred at room temperature overnight under N2 atmosphere. The mixture was then diluted with water (30 mL) and extracted with EtOAc (20 mL×3). The organic layer was washed with brine (30 mL×3), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using column chromatography (dichloromethane:MeOH=30:1) to provide 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxamide (20 mg, yield: 33.3%). 1H-NMR (Methanol-d4, 400 MHz) δ 7.54 (d, J=8.4 Hz, 1H), 7.28˜7.31 (m, 2H), 7.20˜7.24 (m, 2H), 6.90 (s, 1H), 6.82˜6.84 (m, 1H). MS (M+H)+: 318.

Workup

  1. extractionextracted with EtOAc (20 mL×3)
  2. washThe organic layer was washed with brine (30 mL×3)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified

Sources & evidence

ORD record
ord-4d27c1944c9f400592e3ff6ba893aca9
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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