Dimethylformamide → HCID 58204992, compound

HRID 1498343Notes

Reaction equation

HRID 1498343 reaction equation
[H-].[Na+].[CH3:3]N(C=O)C.[CH:8]([N:11]1[C:15]([C:16]2[N:17]=[C:18]3[C:24]4[CH:25]=[CH:26][C:27]([C:29]5[NH:33][C:32]([CH3:34])=[N:31][CH:30]=5)=[CH:28][C:23]=4[O:22][CH2:21][CH2:20][N:19]3[CH:35]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].IC>C1COCC1.O>[CH3:3][N:31]1[CH:30]=[C:29]([C:27]2[CH:26]=[CH:25][C:24]3[C:18]4[N:19]([CH:35]=[C:16]([C:15]5[N:11]([CH:8]([CH3:10])[CH3:9])[N:12]=[CH:13][N:14]=5)[N:17]=4)[CH2:20][CH2:21][O:22][C:23]=3[CH:28]=2)[N:33]=[C:32]1[CH3:34]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58204468HCID 58204468, compound

Product 1

HCID 58204992HCID 58204992, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 100 mL round bottom flask charged with NaH (12 mg, 0.5 mmol) was added DMF (6 mL) dropwise, followed by 271 (100 mg, 0.25 mmol). After stirring for about 1 hour, iodomethane (48 mg, 0.33 mmol) was added dropwise at 0° C. in THF. Then the mixture was allowed to warm up to room temperature slowly and stirred for 2 hours. The reaction mixture was poured into water, extracted with EtOAc, the organic phase was dried over anhydrous Na2SO4, concentrated, then purified by pre-TLC (EtOAc) to give 50 mg (52% Yield) of 282. 1H NMR (CDCl3, 400 MHz): δ8.48 (d, J=8.0 Hz, 1 H), 7.87 (s, 1 H), 7.64 (s, 1 H), 7.48-7.44 (m, 2 H), 7.14 (s, 1 H), 6.04-5.98(m, 1 H), 4.51-4.43 (m, 4 H), 3.62 (s, 3 H), 2.45(s, 3 H ),1.60 (d, J=6.8 Hz, 6 H), and 15 mg (16% yield) of the regioisomer 9-(1,2-dimethyl-1H-imidazol-5-yl)-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 291 1H NMR (CDCl3, 400 MHz): δ8.57 (d, J=8.0 Hz, 1 H), 7.87 (s, 1 H), 7.87 (s, 1 H), 7.69 (s, 1 H), 7.16 (d, J=6.8 Hz, 1 H), 7.06-7.04 (m, 2 H), 6.02-5.96 (m, 1 H), 4.54-4.52 (m, 2 H), 4.48-4.47 (m, 2 H), 3.59 (s, 3 H), 2.46(s, 3 H),1.60 (d, J=6.8 Hz, 6 H). LC-MS: m/z=389 [M+H+].

Workup

  1. stirringstirred for 2 hours
  2. extractionextracted with EtOAc
  3. dry with materialthe organic phase was dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. custompurified by pre-TLC (EtOAc)

Sources & evidence

ORD record
ord-6e7ee6339f544f35bb5ddca0a65f7e31
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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