Cesium carbonate → HCID 57899418, compound

HRID 1024624Notes

Reaction equation

HRID 1024624 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[N:16][N:17]([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:13](=[O:14])[C:12]4[CH:15]=[N:16][N:17]([C:18]5[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:26])=[O:27])[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 57899358HCID 57899358, compound

Product 1

HCID 57899418HCID 57899418, 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

In the last step, a solution of N-(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}-phenyl)-methane sulfonamide (5, 0.5 g, 0.89 mmol) in N,N-dimethylformamide (15 mL) is degassed with argon for 0.5 h. Then 2-amino-5-bromopyridine (0.21 g, 1.22 mmol), cesium carbonate (0.53 g, 1.618 mmol), Pd(dppf)2Cl2 (0.03 g, 0.04 mmol) are added and the resulting solution is degassed with argon for 0.5 h. The reaction mixture is then heated at 100° C. for 6 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-[6-[4-(6-amino-pyridin-3-yl)-phenyl]-5-(4-chloro-phenyl)-4-oxo-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-phenyl}-methane sulfonamide, as a pale yellow solid. 1H NMR (CD3OD, 400 MHz) δ 8.34 (s, 1H), 8.27 (s, 1H), 8.15 (m, 2H), 7.90 (d, 1H), 7.60 (m, 5H), 7.4 (m, 2H), 7.34 (m, 2H), 7.2 (d, 1H), 7.0 (d, 1H), 2.99 (s, 3H); LC-MS calculated for C29H22ClN7O3S (M+H+) 584.1, found 584.1.

Workup

  1. customthe resulting solution 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-532d71951097437d9abc57424d613b21
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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