Cesium fluoride → HCID 68513319, compound

HRID 2241287Notes

Reaction equation

HRID 2241287 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.CC1(C)C(C)(C)OB([C:53]2[CH:54]=[N:55][N:56]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH:57]=2)O1.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:53]3[CH:54]=[N:55][N:56]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH:57]=3)[C:10]=12

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 68513145HCID 68513145, compound

Product 1

HCID 68513319HCID 68513319, compoundYield 70.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A 50 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 (40.0 mg, 0.0566 mmol, prepared in Example 63, step A), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (50.0 mg, 0.170 mmol), Pd(OAc)2 (2.54 mg, 0.0113 mmol), tricyclohexylphosphine (4.76 mg, 0.0170 mmol), cesium fluoride (77.4 mg, 0.510 mmol) and CH3CN (10 mL). The reaction mixture was stirred at 100° C. for 1 hour. The reaction was cooled to room temperature and then the reaction was 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 (29.7 mg, 70.2%). LRMS (APCI neg): >96% purity, 254 nm, m/e 745 (M−1).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customthe reaction was partitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude product
  9. 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-649764518d9d4b25a9b5ad23c0fa0905
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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