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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 886321
Notes
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Reaction equation

HRID 886321 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 58204682
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
Yield 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-3ec2877dddf041a1b67eace4d4d61312
Source dataset
uspto-grants-2012_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08242104B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes