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Dichloromethane → 9-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1498264
Notes
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Reaction equation

HRID 1498264 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
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 58204523
9-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine
Yield 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-dfb680c9aaea4d58a619006dab192d05
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09198918B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes