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

HRID 1521763Notes

Reaction equation

HRID 1521763 reaction equation
[O:1]=[C:2]1[NH:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]3[N:15]=[C:14]([C:16]([OH:18])=O)[CH:13]=[CH:12][C:10]=3[CH:11]=[C:3]12.CN(C([O:26][N:27]1N=N[C:29]2[CH:30]=[CH:31]C=[N:33][C:28]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(P1(N(C)CCCN1)=NC(C)(C)C)CC.CC1ON=C(N)C=1>C1COCC1.CN(C=O)C>[CH3:31][C:30]1[O:26][N:27]=[C:28]([NH:33][C:16]([C:14]2[CH:13]=[CH:12][C:10]3[CH:11]=[C:3]4[C:2](=[O:1])[NH:8][CH2:7][CH2:6][CH2:5][N:4]4[C:9]=3[N:15]=2)=[O:18])[CH:29]=1

Participants

7

Reactant 4

HCID 661723-Amino-5-methylisoxazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 199900182-tert-butylimino-N,N-diethyl-1-methyl-1,3,2lambda5-diazaphosphinan-2-amineHCID 672363426-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 53242193N-(5-Methyl-1,2-oxazol-3-yl)-6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3',2':4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxamideYield 8.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-oxo-7,8,9,10-tetrahydro-6H-pyrido[3′,2′:4,5]pyrrolo[1,2-a][1,4]diazepine-2-carboxylic acid (Intermediate E, 100 mg, 0.41 mmol) in THF (2 mL) and DMF (0.5 mL) is added HATU (171 mg, 0.45 mmol). The mixture is stirred at room temperature for 1 h, after which 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (556 mg, 1.22 mmol) is added. The mixture is stirred at room temperature for 10 min and 5-methyl-3-aminoisoxazole (120 mg, 1.22 mmol) is added. The reaction is stirred at 60° C. for 16 h and is then cooled to room temperature. The mixture is filtered, washing with methanol and the filtrate is concentrated under reduced pressure. 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 (11 mg, 8%). LCMS: 326.20 (M+H+). (System V-med polar)

Workup

  1. stirringThe mixture is stirred at room temperature for 10 min
  2. stirringThe reaction is stirred at 60° C. for 16 h
  3. temperatureis then cooled to room temperature
  4. filtrationThe mixture is filtered
  5. washwashing with methanol
  6. concentrationthe filtrate is concentrated under reduced pressure
  7. customThe residue is purified via preparative HPLC
  8. washa gradient elution from 10-90% acetonitrile/H2O with 0.1% TFA

Sources & evidence

ORD record
ord-40f481b402244c1f997ae6384fbf454c
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

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