Cesium carbonate → HCID 57899425, compound

HRID 1024646Notes

Reaction equation

HRID 1024646 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:17])[C:15]3[N:14]=[CH:13][N:12]([C:18]4[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)=[CH:4][CH:3]=1.Br[C:45]1[CH:46]=[N:47][CH:48]=[N:49][CH:50]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:17])[C:15]3[N:14]=[CH:13][N:12]([C:18]4[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:29]2[CH:30]=[CH:31][C:32]([C:45]3[CH:46]=[N:47][CH:48]=[N:49][CH:50]=3)=[CH:33][CH:34]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 783445-BromopyrimidineHCID 57899376HCID 57899376, compound

Product 1

HCID 57899425HCID 57899425, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of N-(3-{1-(4-chloro-phenyl)-6-oxo-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1,6-dihydro-purin-9-yl}-phenyl)-methane sulfonamide (prepared as described in example 26, 0.500 g, 0.809 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 5-bromopyrimidine (0.195 g, 1.21 mmol), cesium carbonate (0.527 g, 1.61 mmol), Pd(dppf)2Cl2 (0.059 g, 0.08 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is heated to 100° C. for 3 h. The reaction mixture is poured into water and extracted with ethyl acetate (3×). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography to afford N-{3-[1-(4-chloro-phenyl)-6-oxo-2-(4-pyrimidin-5-yl-phenyl)-1,6-dihydro-purin-9-yl]-phenyl}-methane sulfonamide. 1H NMR (DMSO-d6, 400 MHz) δ 10.2 (s, 1H), 9.17 (s, 1H), 9.13 (m, 2H), 8.62 (s, 1H), 7.75 (m, 3H), 7.56 (m, 3H), 7.43-7.50 (m, 5H), 7.25 (d, 1H), 3.05 (s, 3H); LC-MS calculated for C28H20ClN7O3S (M+H+) 570.1, found 569.9.

Workup

  1. customthe resulted mixture is degassed with argon for 0.5 h
  2. additionThe reaction mixture is poured into water
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined organic layer is washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-c9f2d597e7b843668b019839b78ffa24
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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