(1-isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-yl)-carbamic acid benzyl ester → 1-Isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-ylamine

HRID 708209Notes

Reaction equation

HRID 708209 reaction equation
C(OC(=O)[NH:10][C:11]1[N:15]=[C:14]([C:16]2[S:17][C:18]3[CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:33][N:32]([CH2:34][CH2:35][S:36]([CH3:39])(=[O:38])=[O:37])[CH2:31]5)[CH:27]=[CH:26][C:23]=4[C:24]=3[N:25]=2)[N:13]([CH:40]([CH3:42])[CH3:41])[N:12]=1)C1C=CC=CC=1>[Pd]>[CH:40]([N:13]1[C:14]([C:16]2[S:17][C:18]3[CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:31][N:32]([CH2:34][CH2:35][S:36]([CH3:39])(=[O:37])=[O:38])[CH2:33]5)[CH:27]=[CH:26][C:23]=4[C:24]=3[N:25]=2)=[N:15][C:11]([NH2:10])=[N:12]1)([CH3:42])[CH3:41]

Participants

3

Reactant 1

HCID 58204177(1-isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-yl)-carbamic acid benzyl ester

Product 1

HCID 582042261-Isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-ylamine

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst2×

Procedure

A suspension of (1-isopropyl-5-{8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl}-1H-[1,2,4]triazol-3-yl)-carbamic acid benzyl ester (157 mg, 0.25 mmol) in IMS (25 mL) was treated with a slurry of palladium on carbon (50 mg, 50% in water) and the mixture was stirred under an atmosphere of hydrogen for 3 days. More palladium on carbon was added and the mixture stirred for another 18 hours before being filtered through celite. The filtrate was concentrated in vacuo and the residue purified by reverse-phase preparative HPLC (Gemini C18 column, gradient 10-90% MeOH in H2O+0.1% HCO2H) to give 463 as a white solid after freeze drying (43 mg, 35%). LCMS: RT=6.30 min, [M+H]+=489. 1H NMR δ (ppm) (DMSO-d6): 8.22 (1H, d, J=8.18 Hz), 7.14 (1H, dd, J=8.25, 1.81 Hz), 6.99 (1H, d, J=1.77 Hz), 5.67-5.59 (1H, m), 5.54 (2H, s), 4.30 (2H, t, J=5.02 Hz), 3.63-3.50 (3H, m), 3.10 (4H, t, J=6.28 Hz), 3.01 (3H, s), 2.78 (2H, t, J=6.83 Hz), 1.42 (6H, d, J=6.58 Hz). 2 Protons obscured by water peak

Workup

  1. stirringthe mixture stirred for another 18 hours
  2. filtrationbefore being filtered through celite
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue purified by reverse-phase preparative HPLC (Gemini C18 column, gradient 10-90% MeOH in H2O+0.1% HCO2H)

Sources & evidence

ORD record
ord-1ed901290bbb42a29ddc50905dcca8e3
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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