Dichloromethane → HCID 58204793, compound

HRID 1498141Notes

Reaction equation

HRID 1498141 reaction equation
Cl.[CH:2]([N:5]1[C:9]([C:10]2[N:19]=[C:18]3[N:12]([CH2:13][CH2:14][O:15][C:16]4[CH:23]=[C:22]([CH:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)[CH:21]=[CH:20][C:17]=43)[CH:11]=2)=[N:8][CH:7]=[N:6]1)([CH3:4])[CH3:3].BrC1C=CC2C3N(CCOC=2C=1)C=C(C1N(C(C)C)N=CN=1)N=3.B1(C2CCN([C:68]([O:70][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:69])CC=2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CN(C=O)C>[C:71]([O:70][C:68]([N:27]1[CH2:28][CH:29]=[C:24]([C:22]2[CH:21]=[CH:20][C:17]3[C:18]4[N:12]([CH2:13][CH2:14][O:15][C:16]=3[CH:23]=2)[CH:11]=[C:10]([C:9]2[N:5]([CH:2]([CH3:4])[CH3:3])[N:6]=[CH:7][N:8]=2)[N:19]=4)[CH2:25][CH2:26]1)=[O:69])([CH3:74])([CH3:73])[CH3:72]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azuleneHCID 67050785HCID 67050785, compound

Product 1

HCID 58204793HCID 58204793, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Alternatively, 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene hydrochloride can be prepared whereby 8-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (2.1 g, 5.4 mmol), 3,6-dihydro-2H-pyridine-1-N-Boc-4-boronic acid pinacol ester (2.59 g, 8.3 mmol) and potassium carbonate (1.92 g, 13.9 mmol) were mixed with DMF (13 mL) and purged with argon. PdCl2dppf.DCM (310 mg, 0.42 mmol) was added, purging repeated and the mixture heated to 80° C. for 18 h. After cooling the reaction mixture was filtered through Celite®, washing with ethyl acetate, and the filtrate concentrated in vacuo. The residue was partitioned between ethyl acetate and water, the organic layer separated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 2% methanol in ethyl acetate) to give 4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (2.56 g, 96%). LCMS RT=4.79, [M+H]+=477. 1H NMR 400 MHz (CDCl3) δ: 8.45 (1 H, d, J=8.46 Hz), 7.89 (1 H, s), 7.73 (1 H, s), 7.19 (1 H, dd, J=8.37, 1.80 Hz), 7.04 (1 H, d, J=1.87 Hz), 6.15 (1 H, s), 6.04-5.96 (1 H, m), 4.51-4.43 (4 H, m), 4.09 (2 H, d, J=3.68 Hz), 3.64 (2 H, t, J=5.64 Hz), 2.52 (2 H, s), 1.59 (6 H, d, J=6.63 Hz), 1.49 (9 H, s)

Workup

  1. custompurged with argon
  2. custompurging
  3. temperatureAfter cooling the reaction mixture
  4. filtrationwas filtered through Celite®
  5. washwashing with ethyl acetate
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe residue was partitioned between ethyl acetate and water
  8. customthe organic layer separated
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5e035c5540cb4643ba5cb816926aa7d3
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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