Dichloromethane → HCID 68690722, compound

HRID 1157775Notes

Reaction equation

HRID 1157775 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.[N:34]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36][CH:35]=1.ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CO>[CH3:33][O:32][C:5]1[CH:4]=[N:3][C:2]([C:38]2[CH:39]=[N:34][CH:35]=[N:36][CH:37]=2)=[C:7]2[NH:8][CH:9]=[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])[C:6]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 59511493HCID 59511493, compound

Product 1

HCID 68690722HCID 68690722, compoundYield 34.1%

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), pyrimidin-5-ylboronic acid (72.6 mg, 0.586 mmol), 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 4 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-(4-methoxy-7-(pyrimidin-5-yl)-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 (34 mg, 0.066 mmol, 34.1% yield). LCMS: m/e 512.3 (M+H)+, ret time 1.04 min. 1H NMR (500 MHz, MeOD) δ ppm 9.35 (s, 1H) 9.19 (s, 2H) 8.61 (d, J=4.88 Hz, 1H) 8.49 (s, 1H) 8.20 (s, 1H) 8.05-8.11 (m, 1H) 7.83 (d, J=7.93 Hz, 1H) 7.53-7.58 (m, J=7.17, 5.34 Hz, 1H) 4.12 (s, 3H) 3.86-3.90 (m, 2H) 3.63-3.68 (m, 2H) 3.43-3.55 (m, 4H).

Workup

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

Sources & evidence

ORD record
ord-08facea5275642f4b57af2e7264c92ea
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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