Dichloromethane → 4-[2-(2-Isopropyl-5-methoxymethyl-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

HRID 2044539Notes

Reaction equation

HRID 2044539 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:22]([CH3:24])[CH3:23])[N:16]=[C:17]([CH2:19][O:20][CH3:21])[N:18]=1)[N:7]=3.B1([C:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH:37]=2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>COCCOC.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C:45]([O:44][C:42]([N:39]1[CH2:38][CH:37]=[C:36]([C:2]2[CH:26]=[CH:25][C:5]3[C:6]4[N:10]([CH2:11][CH2:12][O:13][C:4]=3[CH:3]=2)[CH:9]=[C:8]([C:14]2[N:15]([CH:22]([CH3:24])[CH3:23])[N:16]=[C:17]([CH2:19][O:20][CH3:21])[N:18]=2)[N:7]=4)[CH2:41][CH2:40]1)=[O:43])([CH3:48])([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 582043878-Bromo-2-(2-isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 582046824-[2-(2-Isopropyl-5-methoxymethyl-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 esterYield 72%

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

8-Bromo-2-(2-isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (250 mg, 0.60 mmol), 3,6-dihydro-2H-pyridine-1-N-Boc-4-boronic acid pinacol ester (370 mg, 1.20 mmol), cesium carbonate (585 mg, 1.79 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium (ii) dichloride, dichloromethane (24 mg, 0.03 mmol) were suspended in DME (4.0 mL), IMS (1.3 mL) and water (0.68 mL) and the reaction mixture purged with argon. The reaction mixture was heated using microwave irradiation in a sealed tube at 140° C. for 20 min. The reaction mixture was washed with water, extracted with DCM (2×15 mL) and the combined organics were washed with brine, dried (Na2SO4) then concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 5% methanol in DCM) to yield 4-[2-(2-Isopropyl-5-methoxymethyl-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 as a brown foam (224 mg, 72%). LCMS: RT=5.08 min, [M+H]+=521

Workup

  1. customIMS (1.3 mL) and water (0.68 mL) and the reaction mixture purged with argon
  2. temperatureThe reaction mixture was heated
  3. custommicrowave irradiation in a sealed tube at 140° C. for 20 min
  4. washThe reaction mixture was washed with water
  5. extractionextracted with DCM (2×15 mL)
  6. washthe combined organics were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationthen concentrated in vacuo
  9. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 5% methanol in DCM)

Sources & evidence

ORD record
ord-8737206eb2f14a318d5ac09693a31d4a
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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