Triethylamine → methyl 4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoate

HRID 44223Notes

Reaction equation

HRID 44223 reaction equation
CS[C:3]1[C:4]2[CH:17]=[CH:16][CH:15]=[CH:14][C:5]=2[NH:6][C:7]2[N:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N:9]=1.[NH:18]([C:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1)=O)[NH2:19].C(N(CC)CC)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl.CO>[N:19]1[N:18]=[C:20]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=2)[N:9]2[C:3]=1[C:4]1[CH:17]=[CH:16][CH:15]=[CH:14][C:5]=1[NH:6][C:7]1[N:13]=[CH:12][CH:11]=[CH:10][C:8]2=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 521998p-Toluenesulfonic acid monohydrateHCID 596004Methyl 4-(hydrazinecarbonyl)benzoateHCID 1682401610-(Methylsulfanyl)-2,4,9-triazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,9,12,14-heptaene

Product 1

HCID 136163852methyl 4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoateYield 44.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 6-(methylthio)-11H-benzo[e]pyrido[3,2-b][1,4]diazepine (2.5 g, 10.4 mmol) in dichloromethane (50 mL) and methanol (20 mL) was added the methyl 4-(hydrazinecarbonyl)benzoate (4.02 g, 20.7 mmol) followed by triethyl amine (1 mL) and p-toluenesulfonic acid monohydrate (3.3 g, 17.3 mmol). The reaction mixture was stirred at 70° C. for 20 hours. The mixture was partitioned between water (100 mL) and dichloromethane (150 mL). The phases were separated and the organic phase was washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated from ethyl acetate, the solid filtered off and dried undet vacuum, yielding the methyl 4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoate as a yellow solid (1.7 g, 44%). M.p.>300° C.; 400 MHz 1H NMR (DMSO-d6) δ: 8.83 (s, 1H), 8.23 (dd, J=4.8, 1.6 Hz, 1H), 8.02 (dt, J=8.8, 1.8 Hz, 2H), 7.97 (dd, J=8.0, 1.6 Hz, 1H), 7.58 (dt, J=8.8, 1.8 Hz, 2H), 7.45 (td, J=5.1, 1.6 Hz, 1H), 7.35 (d, J=7.2 Hz, 1H), 7.2-7.1 (m, 2H), 6.91 (dd, J=8.4, 4.8 Hz, 1H), 3.88 (s, 3H); LCMS [M+H]: 370.

Workup

  1. customThe mixture was partitioned between water (100 mL) and dichloromethane (150 mL)
  2. customThe phases were separated
  3. washthe organic phase was washed with water (50 mL) and brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was triturated from ethyl acetate
  8. filtrationthe solid filtered off
  9. customdried undet vacuum

Sources & evidence

ORD record
ord-79e9a5fb9d124b6f8924805938853b05
Source dataset
uspto-grants-2013_09
Patent number
US08541407B2

Reaction notes

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