Dichloromethane → HCID 68695164, compound

HRID 1157776Notes

Reaction equation

HRID 1157776 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]2[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.[CH3:34][C:35]1[C:39](B2OC(C)(C)C(C)(C)O2)=[C:38]([CH3:49])[O:37][N:36]=1.ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CO>[CH3:34][C:35]1[C:39]([C:2]2[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]3[C:10]([C:11](=[O:31])[C:12]([N:14]4[CH2:19][CH2:18][N:17]([C:20]5[N:24]([C:25]6[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=6)[N:23]=[N:22][N:21]=5)[CH2:16][CH2:15]4)=[O:13])=[CH:9][NH:8][C:7]=23)=[C:38]([CH3:49])[O:37][N:36]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27586563,5-Dimethylisoxazole-4-boronic acid pinacol esterHCID 59511493HCID 59511493, compound

Product 1

HCID 68695164HCID 68695164, compoundYield 54.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

Compounds 1-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (100 mg, 0.195 mmol), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole, 1,1′-Bis(diphenylphosphino)ferrocene palladium (II) chloride complex with dichloromethane (16.06 mg, 0.020 mmol) and Cesium carbonate (127 mg, 0.390 mmol) were combined in Dioxane (2 mL) and Water (0.5 mL). The mixture was heated at 115° C. for 2 hours. After cooling to rt, the mixture was diluted with 10 ml of MeOH and filtered. The filtration was concentrated and purified by HPLC to give 1-(7-(3,5-dimethylisoxazol-4-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (56 mg, 0.106 mmol, 54.3% yield). LCMS: m/e 529.3 (M+H)+, ret time 1.03 min. 1H NMR (500 MHz, MeOD) δ ppm 8.65 (s, 1H) 8.62-8.64 (m, J=4.88 Hz, 1H) 8.23 (s, 1H) 8.08-8.13 (m, 1H) 7.84 (d, J=8.24 Hz, 1H) 7.55-7.60 (m, J=6.71, 4.88 Hz, 1H) 4.15 (s, 3H) 3.87-3.90 (m, 2H) 3.66-3.69 (m, 2H) 3.44-3.54 (m, 4H) 2.41 (s, 3H) 2.22 (s, 3H).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationfiltered
  3. filtrationThe filtration
  4. concentrationwas concentrated
  5. custompurified by HPLC

Sources & evidence

ORD record
ord-67b18b48af634d44a334dee3a4497ce3
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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