Toluene → 6-oxo-N-(quinolin-3-yl)-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamide

HRID 1521764Notes

Reaction equation

HRID 1521764 reaction equation
C[C:2]1(C)[CH2:8][N:7]2[C:9]3[N:15]=[C:14]([C:16]([OH:18])=O)[CH:13]=[CH:12][C:10]=3[CH:11]=[C:6]2[C:5](=[O:19])[NH:4][CH2:3]1.S(Cl)(Cl)=O.[C:25]([C:29]1ON=[C:31]([NH2:34])[CH:30]=1)([CH3:28])([CH3:27])C.C([N:38](CC)C(C)C)(C)C.[C:44]1([CH3:50])C=CC=C[CH:45]=1>>[O:19]=[C:5]1[NH:4][CH2:3][CH2:2][CH2:8][N:7]2[C:9]3[N:15]=[C:14]([C:16]([NH:38][C:30]4[CH:31]=[N:34][C:27]5[C:25]([CH:29]=4)=[CH:28][CH:50]=[CH:44][CH:45]=5)=[O:18])[CH:13]=[CH:12][C:10]=3[CH:11]=[C:6]12

Participants

6

Reactant 5

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 672363209,9-Dimethyl-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid2×

Product 1

HCID 532421996-oxo-N-(quinolin-3-yl)-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamideYield 11%

Procedure

To a suspension of 9,9-dimethyl-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3′,2′:4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid (Intermediate F, 50 mg, 0.18 mmol) in toluene (1 mL) is added thionyl chloride (27 μL, 0.37 mmol) and the mixture is heated at reflux. After 2 h, the mixture is cooled to room temperature and is concentrated under reduced pressure. Toluene (1 mL) is added to the residue and it is concentrated once again under reduced pressure. Toluene (2 mL) is added once more and the volume is reduced by half. 5-tert-butyl-3-aminoisoxazole (51 mg, 0.37 mmol) and N,N-diisopropylethylamine (64 μL, 0.37 mmol) are added and the reaction is stirred at room temperature for 16 h. The reaction mixture is evaporated and the residue is purified via preparative HPLC using a gradient elution from 10-75% acetonitrile/H2O with 0.1% TFA to afford the title compound (8 mg, 11%). LCMS: 396.83 (M+H+).

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux
  3. concentrationis concentrated under reduced pressure
  4. additionToluene (1 mL) is added to the residue and it
  5. concentrationis concentrated once again under reduced pressure
  6. additionToluene (2 mL) is added once more
  7. customThe reaction mixture is evaporated
  8. customthe residue is purified via preparative HPLC
  9. washa gradient elution from 10-75% acetonitrile/H2O with 0.1% TFA

Sources & evidence

ORD record
ord-2b156a7c74d6431ab7b88a2f21c96bf4
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

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