Cesium fluoride → HCID 68512288, compound

HRID 2241292Notes

Reaction equation

HRID 2241292 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([C:31]2[C:32](=[O:44])[N:33]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:34]=[CH:35][CH:36]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:16]=[C:17](I)[C:10]=12.[CH3:45][N:46]1[CH:50]=[C:49](B2OC(C)(C)C(C)(C)O2)[CH:48]=[N:47]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2].CC#N>[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([C:31]2[C:32](=[O:44])[N:33]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:34]=[CH:35][CH:36]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:16]=[C:17]([C:49]3[CH:48]=[N:47][N:46]([CH3:45])[CH:50]=3)[C:10]=12

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 68513145HCID 68513145, compound

Product 1

HCID 68512288HCID 68512288, compoundYield 50.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A 100 mL round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (50.0 mg, 0.0708 mmol, prepared in Example 63, step A), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (44.2 mg, 0.212 mmol), Pd(OAc)2 (3.18 mg, 0.0142 mmol), tricyclohexylphosphine (5.95 mg, 0.0212 mmol), cesium fluoride (96.8 mg, 0.637 mmol) and CH3CN (10 mL). The reaction mixture was stirred at 100° C. 1 hour. The reaction was cooled to room temperature and partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (23.8 mg, 50.9%). LRMS (APCI pos): >95% purity, 254 nm, m/e 661 (M+1).

Workup

  1. custom1 hour
  2. temperatureThe reaction was cooled to room temperature
  3. custompartitioned between EtOAc and H2O
  4. customThe phases were separated
  5. extractionthe aqueous phase was re-extracted with EtOAc
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a crude product
  10. customThe crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1

Sources & evidence

ORD record
ord-973d79e3aa004c2db26193eb96c8fb98
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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