Dimethylformamide → HCID 57899369, compound

HRID 1024612Notes

Reaction equation

HRID 1024612 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3C=N[N:17]([C:18]4[CH:19]=[C:20]([S:24]([NH2:27])(=[O:26])=[O:25])[CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)=[CH:4][CH:3]=1.[NH2:43][C:44]1[CH:49]=[CH:48][C:47](Br)=[CH:46][N:45]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:57][N:58](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]>[NH2:43][C:44]1[N:45]=[CH:46][C:47]([C:31]2[CH:32]=[CH:33][C:28]([C:9]3[N:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[C:13](=[O:14])[C:12]4[N:58]=[CH:57][N:17]([C:18]5[CH:19]=[C:20]([S:24]([NH2:27])(=[O:25])=[O:26])[CH:21]=[CH:22][CH:23]=5)[C:11]=4[N:10]=3)=[CH:29][CH:30]=2)=[CH:48][CH:49]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 706222-Amino-5-bromopyridineHCID 57899416HCID 57899416, compound

Product 1

HCID 57899369HCID 57899369, compound

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

A solution of 3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl}-benzene sulfonamide (0.300 g, 0.496 mmol) in N,N-dimethylformamide (25 mL) is degassed with argon for 0.5 h. Then 2-amino-5-bromopyridine (0.128 g, 0.745 mmol), cesium carbonate (0.323 g, 0.993 mmol), Pd(dppf)2Cl2 (0.036 g, 0.049 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 4 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 3-[2-[4-(6-amino-pyridin-3-yl)-phenyl]-1-(4-chloro-phenyl)-6-oxo-1,6-dihydro-purin-9-yl]-benzene sulfonamide. 1H NMR (DMSO-d6, 400 MHz) δ 8.66 (s, 1H), 8.23 (s, 1H), 8.07 (m, 1H), 7.94 (m, 1H), 7.83 (m, 1H), 7.67 (m, 1H), 7.58 (m, 2H), 7.35-7.48 (m, 10H), 6.47 (d, 1H), 6.15 (br, 1H); LC-MS calculated for C28H20ClN7O3S (M+H+) 570.1, found 570.2.

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-d133dcc7684d46979dfcbd7cf043f3b7
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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