Hexahydro-1,4-diazepine → HCID 58203876, compound

HRID 1190554Notes

Reaction equation

HRID 1190554 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:16]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[N:17]=[CH:18][N:19]=4)[S:8][C:7]=3[C:6]=2[N:28]=1.[NH:29]1[CH2:35][CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(O[Na])(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[N:29]1([C:2]2[CH:3]=[CH:4][C:5]3[O:14][CH2:13][CH2:12][C:11]4[CH:10]=[C:9]([C:15]5[N:16]([C:20]6[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=6[F:27])[N:17]=[CH:18][N:19]=5)[S:8][C:7]=4[C:6]=3[N:28]=2)[CH2:35][CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 68163Hexahydro-1,4-diazepineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 579003099-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azuleneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 58203876HCID 58203876, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
112 °C

Procedure

9-Chloro-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 (416 mg, 1.0 mmol), 1,4-diazepane (120 mg, 1.2 mmol), Pd2(dba)3 (210 mg, 0.3 mmol), Xphos (142 mg, 0.3 mmol), t-BuONa (576 mg, 6 mmol) and dioxane (6 mL) were added into a 10 mL of sealed tube, and the mixture was heated by microwave at 112° C. for 7 min under N2. The reaction mixture was filtered to gather the solution. The water was added and extracted by DCM (50 mL×3). The combined organic layers were dried over Na2SO4, concentrated in vacuo, and separated by column (DCM/EtOAc=4:1) to get 350 (120 mg, yield: 25%). 1HNMR (DMSO-d6, 400 MHz): δ8.04 (s, 1H), 7.97 (s, 1H), 7.67-7.65 (m, 1H), 7.50-7.46 (m, 1H), 7.20 (t, J=8 Hz, 1H), 7.02 (s, 1H), 6.97 (d, J=8.8 Hz, 1H), 6.36 (d, J=8.8 Hz, 1H), 3.92 (d, J=4.4 Hz, 2H), 3.37-3.31 (m, 4H), 2.87 (d, J=4.4 Hz, 4H), 2.72 (s, 2H), 2.57 (s, 2H), 1.59 (s, 2H). ESI-MS: m/z=481 [M+H+]

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionThe water was added
  3. extractionextracted by DCM (50 mL×3)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customseparated by column (DCM/EtOAc=4:1)

Sources & evidence

ORD record
ord-d52b6dce4ea540729357c543fec23118
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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