Cesium fluoride → 4-[4-Amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one

HRID 1056945Notes

Reaction equation

HRID 1056945 reaction equation
[F-].[Cs+].Br[C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1[O:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[F:22].[CH3:23][N:24]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[C:27]2=[CH:39][N:40]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[N:41]=[C:26]2[C:25]1=[O:50]>C(O)CCC.O.C(OCC)(=O)C.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.Cl[Pd]Cl>[NH2:8][C:7]1[CH:9]=[CH:10][C:4]([C:28]2[C:27]3[C:26](=[N:41][N:40]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:47])([CH3:49])[CH3:48])[CH:39]=3)[C:25](=[O:50])[N:24]([CH3:23])[CH:29]=2)=[C:5]([O:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[C:6]=1[N+:11]([O-:13])=[O:12]

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 1180939204-Bromo-3-(2,4-difluorophenoxy)-2-nitroanilineHCID 1317364506-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one

Product 1

HCID 1234126994-[4-Amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-oneYield 50%

Reagents, catalysts & solvents 4

HCID 86647055di-tert-butyl(4-dimethylaminophenylphosphine) dichloropalladium(II)CatalystHCID 2631-ButanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-(di-tert-butylphosphino)-N,N-dimethylaniline-dichloropalladium (2:1) (22.3 mg, 0.0314 mmol), cesium fluoride (1.11 g, 7.34 mmol), 4-bromo-3-(2,4-difluorophenoxy)-2-nitroaniline (724 mg, 2.10 mmol), and 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (850 mg, 2.097 mmol) in 1-butanol (9.5 mL) and water (2.2 mL) was degassed with nitrogen for 5 min and heated at 100° C. for 2 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated and washed with brine, dried with magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (50% EtOAc/hexanes to 100% EtOAc) gave the desired product (0.57 g, 50%). LCMS calculated for C25H28F2N5O5Si (M+H)+: m/z=544.2. found: 544.1.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customPurification by flash column chromatography (50% EtOAc/hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-b82ce9447cc74328b366f921faf8847d
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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