Cesium carbonate → HCID 59511495, compound

HRID 1157793Notes

Reaction equation

HRID 1157793 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]=[CH:38][C:37]([NH2:40])=[N:36][CH:35]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:33][O:32][C:5]1[CH:4]=[N:3][C:2]([NH:40][C:37]2[CH:38]=[CH:39][N:34]=[CH:35][N:36]=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 10796Cesium carbonateHCID 689584-AminopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59511493HCID 59511493, compound

Product 1

HCID 59511495HCID 59511495, compoundYield 4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

A suspension of 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-4-amine (55.7 mg, 0.586 mmol), Tris(dibenzylideneacetone)dipalladium(0) (8.94 mg, 9.76 μmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (11.29 mg, 0.020 mmol) and Cesium carbonate (127 mg, 0.390 mmol) in Dioxane (2 mL) was heated at 115° C. for 4 hours. After cooling to rt, the mixture was diluted with MeOH and filtered. The filtrate was concentrated and purified by prep. HPLC to give 1-(4-methoxy-7-(pyrimidin-4-ylamino)-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 (4.1 mg, 7.79 μmol, 3.99% yield). LCMS: m/e 527.3 (M+H)+, ret time 1.02 min. 1H NMR (500 MHz, MeOD) δ ppm 8.87 (s, 1H) 8.61 (d, J=3.66 Hz, 1H) 8.49 (d, J=6.10 Hz, 1H) 8.42 (s, 1H) 8.03-8.10 (m, 1H) 7.83 (d, J=7.94 Hz, 1H) 7.67 (s, 1H) 7.51-7.56 (m, 2H) 4.02 (s, 3H) 3.83-3.90 (m, 2H) 3.62-3.67 (m, 2H) 3.43-3.56 (m, 4H).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. custompurified by prep

Sources & evidence

ORD record
ord-e1418f32fac94c1f96138b7f793311a4
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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