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

HRID 1521765Notes

Reaction equation

HRID 1521765 reaction equation
[CH3:1][CH:2]1[N:8]2[C:9]3[N:15]=[C:14]([C:16]([OH:18])=O)[CH:13]=[CH:12][C:10]=3[CH:11]=[C:7]2[C:6](=[O:19])[NH:5][CH2:4][CH2:3]1.ClC(N(C)C)=C(C)C.[CH2:28]([C:35]1[O:39][N:38]=[C:37]([NH2:40])[CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.N1C=CC=CC=1>C(Cl)Cl>[CH2:28]([C:35]1[O:39][N:38]=[C:37]([NH:40][C:16]([C:14]2[CH:13]=[CH:12][C:10]3[CH:11]=[C:7]4[C:6](=[O:19])[NH:5][CH2:4][CH2:3][CH:2]([CH3:1])[N:8]4[C:9]=3[N:15]=2)=[O:18])[CH:36]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 672354765-Benzylisoxazol-3-amine2×HCID 6723721510-Methyl-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 53242177N-(5-benzyl-1,2-oxazol-3-yl)-10-methyl-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamideYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 10-methyl-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3′,2′:4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid (Intermediate G, 75 mg, 0.29 mmol) in CH2Cl2 (5 mL) is added 1-chloro-N,N,2-trimethylpropenylamine (138 μL, 1.01 mmol) and the mixture is stirred at room temperature for 30 min. 5-benzyl-1,2-oxazol-3-amine (Intermediate W, 252 mg, 1.45 mmol) and pyridine (94 μL, 1.16 mmol) are added and the reaction is stirred at room temperature for 20 h. The mixture is concentrated under reduced pressure and the residue is purified via preparative HPLC using a gradient elution from 10-90% acetonitrile/H2O with 0.1% TFA to afford the title compound (19 mg, 16%). LCMS: 416.20 (M+H+). (System V-med polar)

Workup

  1. stirringthe reaction is stirred at room temperature for 20 h
  2. concentrationThe mixture is concentrated under reduced pressure
  3. customthe residue is purified via preparative HPLC
  4. washa gradient elution from 10-90% acetonitrile/H2O with 0.1% TFA

Sources & evidence

ORD record
ord-d3f4fcd682a0418a806131ab6a17224d
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

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