Toluene → HCID 58574479, compound

HRID 1619427Notes

Reaction equation

HRID 1619427 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12](O)=[O:13])=[CH:9][CH:10]=2)[N:5]=[C:4]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:3]12.C1(C)C=CC=CC=1.[F:28][C:29]1[CH:39]=[CH:38][C:32](/[C:33](=[N:36]\[H])/[NH:34]O)=[CH:31][CH:30]=1>O=S(Cl)Cl.N1C=CC=CC=1>[F:28][C:29]1[CH:39]=[CH:38][C:32]([C:33]2[N:36]=[C:12]([C:8]3[CH:7]=[C:6]4[C:11]([C:2](=[O:1])[N:3]5[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C:4]5=[N:5]4)=[CH:10][CH:9]=3)[O:13][N:34]=2)=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 71306156,8,9,10,11,13-Hexahydro-13-oxo-7H-azocino[2,1-b]quinazoline-3-carboxylic acidHCID 178506503HCID 178506503, compound

Product 1

HCID 58574479HCID 58574479, compoundYield 11.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 13-oxo-7,8,9,10,11,13-hexahydro-6H-azocino[2,1-b]quinazoline-3-carboxylic acid (75 mg, 0.28 mmol) in SOCl2 (3 mL) was stirred at reflux for 0.5 h. The excess SOCl2 was removed and the residue was diluted with toluene (5 mL). The toluene solution was added dropwise to a solution of (E)-4-fluoro-N-hydroxybenzimidamide (51 mg, 0.33 mmol) in pyridine (2 mL). After stirring at room temperature for 0.5 h, the mixture was heated and kept at 60° C. overnight. The reaction mixture was concentrated and then diluted with water (25 mL). The aqueous mixture was extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with brine and dried over Na2SO4. After concentration, the crude product was purified by column chromatography to give the desired product (13 mg). MS (ESI): 391 (MH+); 1H NMR (300 MHz, CDCl3) δ 8.52 (s, 1H), 8.45-8.42 (d, J=7.68 Hz, 1H), 8.25-8.18 (m, 3H), 7.23-7.20 (t, J=7.8 Hz, 2H), 4.38 (broad, 2H), 3.11-3.09 (m, 2H), 2.03 (broad, 2H), 1.94 (broad, 2H), 1.64 (broad, 2H), 1.48 (broad, 2H).

Workup

  1. temperatureat reflux for 0.5 h
  2. customThe excess SOCl2 was removed
  3. additionthe residue was diluted with toluene (5 mL)
  4. temperaturethe mixture was heated
  5. waitkept at 60° C. overnight
  6. concentrationThe reaction mixture was concentrated
  7. additiondiluted with water (25 mL)
  8. extractionThe aqueous mixture was extracted with ethyl acetate (2×25 mL)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationAfter concentration
  12. customthe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-86d79f0408824111b22419354b443061
Source dataset
uspto-grants-2014_07
Patent number
US08772301B2

Reaction notes

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