Cesium carbonate → HCID 57899410, compound

HRID 1024611Notes

Reaction equation

HRID 1024611 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.[NH2:44][C:45]1[CH:50]=[CH:49][C:48](Br)=[CH:47][N:46]=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]>[NH2:44][C:45]1[N:46]=[CH:47][C:48]([C:32]2[CH:33]=[CH:34][C:29]([C:9]3[N:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[C:16](=[O:17])[C:15]4[N:14]=[CH:13][N:12]([C:18]5[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=5)[C:11]=4[N:10]=3)=[CH:30][CH:31]=2)=[CH:49][CH:50]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 706222-Amino-5-bromopyridineHCID 57899376HCID 57899376, compound

Product 1

HCID 57899410HCID 57899410, 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, 0.700 g, 1.13 mmol) in N,N-dimethylformamide (15 mL) is degassed with argon for 0.5 h. Then 2-amino-5-bromopyridine (0.290 g, 1.69 mmol), cesium carbonate (0.740 g, 2.26 mmol), Pd(dppf)2Cl2 (0.040 g, 0.056 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is then heated at 100° C. for 3 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3×). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by preparative HPLC to afford N-{3-[2-[4-(6-amino-pyridin-3-yl)-phenyl]-1-(4-chloro-phenyl)-6-oxo-1,6-dihydro-purin-9-yl]-phenyl}-methane sulfonamide, as a yellow solid. 1H NMR (CD3OD, 400 MHz) δ 8.51 (s, 1H), 8.22 (m, 1H), 8.12 (d, 1H), 7.93 (d, 1H), 7.55 (m, 6H), 7.37 (m, 2H), 7.34 (m, 2H), 7.32 (d, 1H), 7.10 (d, 1H), 3.0 (s, 3H); LC-MS calculated for C29H22ClN7O3S (M+H+) 584.1, found 583.9.

Workup

  1. customthe resulted mixture is degassed with argon for 0.5 h
  2. temperatureThe reaction mixture is cooled to rt
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-2189ad5498b34f1090f81ff7caae0427
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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