Dichloromethane → HCID 58204523, compound

HRID 886207Notes

Reaction equation

HRID 886207 reaction equation
[NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].[H-].[Na+].[CH:9]([N:12]1[C:16]([C:17]2[N:18]=[C:19]3[C:25]4[CH:26]=[CH:27][C:28]([C:30](OC)=O)=[CH:29][C:24]=4[O:23][CH2:22][CH2:21][N:20]3[CH:34]=2)=[N:15][CH:14]=[N:13]1)([CH3:11])[CH3:10].C(Cl)Cl.S(Cl)(Cl)=O>O1CCCC1.C1COCC1.CN(C=O)C>[CH3:5][C:2]1([CH3:6])[CH2:3][O:4][C:30]([C:28]2[CH:27]=[CH:26][C:25]3[C:19]4[N:20]([CH:34]=[C:17]([C:16]5[N:12]([CH:9]([CH3:11])[CH3:10])[N:13]=[CH:14][N:15]=5)[N:18]=4)[CH2:21][CH2:22][O:23][C:24]=3[CH:29]=2)=[N:1]1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 118072-Amino-2-methyl-1-propanolHCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 58204510methyl 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-9-carboxylate

Product 1

HCID 58204523HCID 58204523, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

2-Amino-2-methyl-1-propanol (0.20 g, 2.3 mmol) was dissolved in tetrahydrofuran (2.2 mL) and NaH (60% in mineral oil, 0.0942 g) was added. The resulting mixture was stirred for 1 h at room temp. To this mixture was added methyl 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-9-carboxylate 184 (0.40 g, 1.1 mmol) in THF/DMF (1:1, 10 mL). The entire reaction mixture was stirred at ambient temperature overnight. The reaction was quenched with water and diluted with EtOAc. Extracted, dried over MgSO4, filtered and concentrated. Dissolved in Methylene chloride (10 mL, 200 mmol) and cooled to at 0° C. and treated with thionyl chloride (0.314 mL, 4.30 mmol) dropwise. Following the addition, the reaction was warmed to room temp and stirred for 3 h. Concentrated in vacuo and purified by reverse phase HPLC to provide 199 (209 mg, 48% yield). LC/MS (ESI+): m/z 393 (M+H). 1H NMR (400 MHz, DMSO) δ 8.47 (d, J=8.4, 1H), 7.99 (s, 1H), 7.92 (d, J=3.5, 1H), 7.59 (dd, J=8.4, 1.6, 1H), 7.45 (d, J=1.6, 1H), 5.85 (dt, J=13.2, 6.6, 1H), 4.55 (dd, J=10.6, 6.4, 4H), 4.12 (s, 2H), 1.49 (d, J=6.6, 6H), 1.30 (s, 6H)

Workup

  1. customThe entire reaction mixture
  2. stirringwas stirred at ambient temperature overnight
  3. customThe reaction was quenched with water
  4. additiondiluted with EtOAc
  5. extractionExtracted
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. temperaturecooled to at 0° C.
  10. additionthe addition
  11. temperaturethe reaction was warmed to room temp
  12. stirringstirred for 3 h
  13. concentrationConcentrated in vacuo
  14. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-43828a596eec486bb616e7594a6344f6
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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