4-Fluorophenylboronic acid → 5-(3-fluoro-4-(3-(4-fluorophenyl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 2241304Notes

Reaction equation

HRID 2241304 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:28]2[C:29](=[O:42])[N:30]([CH3:41])[C:31]([NH:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[N:32][CH:33]=2)[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.[F:43][C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:28]2[C:29](=[O:42])[N:30]([CH3:41])[C:31]([NH:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[N:32][CH:33]=2)[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:47]3[CH:48]=[CH:49][C:44]([F:43])=[CH:45][CH:46]=3)[C:10]=12

Participants

7

Reactant 3

HCID 2856454-Fluorophenylboronic acidHCID 433294Lithium ChlorideHCID 685142125-(3-fluoro-4-(3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Product 1

HCID 685153815-(3-fluoro-4-(3-(4-fluorophenyl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 5-(3-fluoro-4-(3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.025 g, 0.0371 mmol; prepared according to the procedure of Example 86, Step E), 4-fluorophenylboronic acid (0.006 g, 0.04 mmol), Pd(PPh3)4 (0.002 g, 0.002 mmol) and lithium chloride (0.006 g, 0.15 mmol) in dioxane (1 mL) and 2 M aqueous Na2CO3 (1 mL) was stirred at 110° C. for 35 minutes and then at ambient temperature overnight. The reaction mixture was partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated to yield 0.031 g crude product as a yellow gum. The crude material was used without further purification in the following step. LRMS (APCI pos) m/e 643 (M+1).

Workup

  1. customprepared
  2. customat ambient temperature
  3. customovernight
  4. customThe reaction mixture was partitioned between EtOAc and H2O
  5. customThe layers were separated
  6. extractionthe aqueous layer was re-extracted with EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-69cc80244e5748bfaabe4987db2ac13a
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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