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

HRID 2241236Notes

Reaction equation

HRID 2241236 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16](Cl)=[C:11]3[C:10]([CH3:18])=[N:9]2)=[CH:5][CH:4]=1.[F:21][C:22]1[CH:23]=[C:24]([C:29]2[C:30](=[O:43])[N:31]([CH3:42])[C:32]([NH:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[N:33][CH:34]=2)[CH:25]=[CH:26][C:27]=1[OH:28].C(=O)([O-])[O-].[K+].[K+].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[F:21][C:22]1[CH:23]=[C:24]([C:29]2[C:30](=[O:43])[N:31]([CH3:42])[C:32]([NH:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[N:33][CH:34]=2)[CH:25]=[CH:26][C:27]=1[O:28][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:19]=[CH:20][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:9]=[C:10]([CH3:18])[C:11]=12

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 23665647Potassium tert-butoxideHCID 673501215-(3-fluoro-4-hydroxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-oneHCID 685123991-(4-methoxybenzyl)-4-chloro-3-methyl-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 685152335-(3-fluoro-4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-oneYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a 10 mL round bottom flask was added 1-(4-methoxybenzyl)-4-chloro-3-methyl-1H-pyrazolo[3,4-b]pyridine (18.7 mg, 0.065 mmol; prepared according to the procedure of Example 43, Step E), 5-(3-fluoro-4-hydroxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (13.5 mg, 0.043 mmol) and the solids were dissolved in DMF (0.5 mL). Potassium carbonate (9.0 mg, 0.065 mmol) was added followed by a 1M solution of potassium t-butoxide in THF (0.065 mL, 0.065 mmol), and the mixture was stirred at 110° C. for 18 hours. The reaction mixture was cooled to room temperature and then partitioned between water (5 mL) and ethyl acetate (10 mL). The organic layer washed with water, brine, dried over Na2SO3 and concentrated to afford 24.3 mg of crude oil. The crude product was triturated with ether to afford the desired product (16 mg, 65%) as a tan solid. LRMS (APCI pos) m/e 563.3 (M+1).

Workup

  1. customprepared
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between water (5 mL) and ethyl acetate (10 mL)
  4. washThe organic layer washed with water, brine
  5. dry with materialdried over Na2SO3
  6. concentrationconcentrated
  7. customto afford 24.3 mg of crude oil
  8. customThe crude product was triturated with ether

Sources & evidence

ORD record
ord-57c46536b29943a2ace5e89fe38feec7
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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