Carbon Disulfide → HCID 59713676, compound

HRID 2223083Notes

Reaction equation

HRID 2223083 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[C:6]2[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:5]=2[N:4]([CH3:20])[C:3]1=[O:21].[C:22](=S)=[S:23].CCN=C=NCCCN(C)C.CCN(CC)CC>C1COCC1>[Cl:19][C:16]1[CH:17]=[CH:18][C:5]2[N:4]([CH3:20])[C:3](=[O:21])[CH:2]([N:1]=[C:22]=[S:23])[N:8]=[C:7]([C:9]3[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=3)[C:6]=2[CH:15]=1

Participants

6

Reactant 4

HCID 6348Carbon DisulfideHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 59713845HCID 59713845, compound

Product 1

HCID 59713676HCID 59713676, compoundYield 42.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

As illustrated in the scheme above, a solution of 3-amino-7-chloro-1,3-dihydro-1-methyl-5-(3-pyridinyl)-2H-1,4benzodiazepin-2-one (1.36 g, 4.52 mmol) in dry THF (55 mL) was cooled to −15° C. Carbon disulfide (2.7 mL, 45 mmol) was added, followed by EDCI (1.73 g, 9.03 mmol). The mixture was stirred for 10 min., and then Et3N (1.26 mL, 9.04 mmol) was added. The reaction was stirred for 16 h while it was allowed to slowly warm to room temperature. The precipitated solid was removed by filtration and was washed well with CH2Cl2 and then discarded. The filtrate was concentrated in vacuo, and the residue was dissolved in CH2Cl2. The organic phase was washed with water, saturated NaHCO3, and brine, and was then dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the crude product by silica gel column chromatography (3:1 CH2Cl2:EtOAc) provided the title compound as a solid (0.652 g, 42%). 1H-NMR (CDCl3): δ 8.75 (s, 2H), 8.12 (dt, J=2.0 Hz, J=8.0 Hz, 1H), 7.63 (dd, J=2.0 Hz, J=8.8 Hz, 1H), 7.43 (dd, J=4.8 Hz, J=8.0 Hz, 1H), 7.39 (d, J=8.8 Hz, 1H), 7.33 (d, J=2.4 Hz, 1H), 5.22 (s, 1H), 3.50 (s, 3H). MS (ESI) (M+H)+=343.

Workup

  1. stirringThe reaction was stirred for 16 h while it
  2. temperatureto slowly warm to room temperature
  3. customThe precipitated solid was removed by filtration
  4. washwas washed well with CH2Cl2
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutionthe residue was dissolved in CH2Cl2
  7. washThe organic phase was washed with water, saturated NaHCO3, and brine
  8. dry with materialwas then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the crude product by silica gel column chromatography (3:1 CH2Cl2:EtOAc)

Sources & evidence

ORD record
ord-f24e026972194972bf4174be620f0cc7
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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