Water → 1-(5-{2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-yl}-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-ethanone

HRID 1190513Notes

Reaction equation

HRID 1190513 reaction equation
[CH:1]12[CH2:7][CH:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]1[CH:9]=[CH:10][C:11]2[O:20][CH2:19][CH2:18][C:17]3[CH:16]=[C:15]([C:21]4[N:22]([C:26]5[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=5[F:33])[N:23]=[CH:24][N:25]=4)[S:14][C:13]=3[C:12]=2[N:34]=1.[C:35](Cl)(=[O:37])[CH3:36].CCN(C(C)C)C(C)C.O>C1COCC1>[F:33][C:27]1[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=1[N:22]1[C:21]([C:15]2[S:14][C:13]3[C:12]4[N:34]=[C:8]([N:2]5[CH2:3][CH:4]6[CH2:7][CH:1]5[CH2:6][N:5]6[C:35](=[O:37])[CH3:36])[CH:9]=[CH:10][C:11]=4[O:20][CH2:19][CH2:18][C:17]=3[CH:16]=2)=[N:25][CH:24]=[N:23]1

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 582039709-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene

Product 1

HCID 582041411-(5-{2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-yl}-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-ethanoneYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 310 (479 mg, 1.0 mmol), Acetyl chloride (100 mg, 1.2 mmol), DIPEA (260 mg, 2.0 mmol) was dissolved in THF (10 mL). The reaction mixture was stirred at r.t. for 1 hour. LC-MS indicated the reaction was completed. To the reaction mixture was added 20 mL of water, the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and concentrated to dryness. The crude was purified by pre-HPLC to afford 311 (78.1 mg, yield: 15%). 1HNMR (DMSO-d6, 400 MHz): δ8.27 (s, 1H), 7.91-7.90 (m, 1H), 7.74 (s, 1H), 7.43-7.39 (m, 1H), 7.23-7.20 (m, 2H), 6.48 (t, J=4.4 Hz, 1H), 4.77 (s, 2H), 3.53 (s, 2H), 3.53-3.32 (m, 4H), 3.19 (s, 2H), 1.96 (s, 3H), 1.23 (s, 2H). ESI-MS: m/z=521 [M+H+]

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated to dryness
  4. customThe crude was purified by pre-HPLC

Sources & evidence

ORD record
ord-9f95dc9cd98e4faaafcaff9ed68cf287
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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