Methanol → 2-(4-isopropyl-4H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carboxylic acid methyl ester

HRID 1848993Notes

Reaction equation

HRID 1848993 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]=[C:8]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[CH:17]=[N:16][N:15]=4)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C1CCN2C(=NCCC2)CC1.O1C[CH2:57][O:56][CH2:55]C1.C[OH:60]>CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[CH3:55][O:56][C:57]([C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]=[C:8]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[CH:17]=[N:16][N:15]=4)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)=[O:60]

Participants

8

Reactant 5

HCID 887MethanolHCID 312751,4-DioxaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 582038068-Bromo-2-(4-isopropyl-4H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Product 1

HCID 582040372-(4-isopropyl-4H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carboxylic acid methyl esterYield 54%

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with 8-bromo-2-(4-isopropyl-4H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (1.0 g, 2.56 mmol), molybdenum hexacarbonyl (338 mg, 1.28 mmol), Herrmann's catalyst [trans-bis(acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II)] (122 mg, 0.13 mmol), tri-tert-butylphosphonium tetrafluoroborate (75 mg, 0.26 mmol), DBU (0.38 mL, 2.56 mmol), 1,4-dioxan (6 mL) and MeOH (6 mL), flushed with nitrogen then sealed. The mixture was heated at 150° C. for 45 minutes using microwave irraditation then filtered through a pad of Celite®, washing the pad with MeOH. The filtrate was concentrated in vacuo and the residue purified by flash chromatography (SiO2, 0-5% MeOH in EtOAc) to give the title compound as a yellow solid (0.51 g, 54%). LCMS: RT=4.28 min, [M+H]+=371

Workup

  1. customflushed with nitrogen
  2. customthen sealed
  3. filtrationthen filtered through a pad of Celite®
  4. washwashing the pad with MeOH
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue purified by flash chromatography (SiO2, 0-5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-76649b1fdb744773aa9d93804d6a50ae
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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