4-Methoxybenzylamine → HCID 58204043, compound

HRID 1849066Notes

Reaction equation

HRID 1849066 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.[CH3:29][O:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=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>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[N:16]1[C:15]([C:9]2[S:8][C:7]3[C:6]4[N:28]=[C:2]([NH:36][CH2:35][C:34]5[CH:37]=[CH:38][C:31]([O:30][CH3:29])=[CH:32][CH:33]=5)[CH:3]=[CH:4][C:5]=4[O:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)=[N:19][CH:18]=[N:17]1

Participants

7

Reactant 4

HCID 754524-MethoxybenzylamineHCID 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 58204043HCID 58204043, compoundYield 77.3%

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 (1.23 g, 3.0 mmol), 4-Methoxy-benzylamine (493 mg, 3.6 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) was added in a 10 mL of sealed tube, and the reaction mixture was heated by microwave at 112° C. for 7 min under N2. The reaction mixture was filtered to gather the solution. Then water was added into the solution and extracted by DCM (50 mL×3). The combined organic layer was dried by Na2SO4, concentrated in vacuo, separated by TLC (DCM: EtOAc=4:1) to give {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}-(4-methoxy-benzyl)-amine (1.2 g, yield: 77%). 1H NMR (DMSO-d6, 400 MHz): δ 8.36 (s, 1 H), 7.96 (d, J=2.0 Hz, 1 H), 7.69 (s, 1 H), 7.39 (s, 1 H), 7.31 (s, 1 H), 7.29 (s, 2 H), 7.14 (s, 1 H), 6.97-6.90 (m, 3 H), 6.46 (d, J=8.8 Hz, 1 H), 4.34 (d, J=6.4 Hz, 2 H), 4.20 (s, 2 H), 3.77 (s, 3 H), 3.12 (s, 2 H). LC-MS (ESI): m/z=518 [M+H]+

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionThen water was added into the solution
  3. extractionextracted by DCM (50 mL×3)
  4. dry with materialThe combined organic layer was dried by Na2SO4
  5. concentrationconcentrated in vacuo
  6. customseparated by TLC (DCM: EtOAc=4:1)

Sources & evidence

ORD record
ord-e5245d6f77204cab9f8a0aab25b9d037
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

Loading…