Dichloromethane → tert-butyl 7-[6-(2,6-difluoro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1778786Notes

Reaction equation

HRID 1778786 reaction equation
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21](I)[C:16]2=[CH:15][N:14]=1.CC1(C)C(C)(C)OB([C:31]2[CH:40]=[C:39]3[C:34]([CH2:35][CH2:36][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:38]3)=[CH:33][CH:32]=2)O1.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21]([C:31]3[CH:40]=[C:39]4[C:34]([CH2:35][CH2:36][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:38]4)=[CH:33][CH:32]=3)[C:16]2=[CH:15][N:14]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 53302321tert-Butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 178493522HCID 178493522, compound

Product 1

HCID 178493512tert-butyl 7-[6-(2,6-difluoro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 6-(2,6-difluoro-3,5-dimethoxyphenyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (16.7 mg, 0.0400 mmol), tert-butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (17.96 mg, 0.05000 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (2.0 mg, 0.0024 mmol) and potassium phosphate (25.5 mg, 0.120 mmol) in 1,4-dioxane (0.50 mL) and water (0.15 mL) in a reaction vial was sealed, and degassed and recharged with nitrogen for three times. The mixture was stirred at 115° C. for 3 h. After cooling, the mixture was diluted with methanol, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+=524.1.

Workup

  1. customin a reaction
  2. customvial was sealed
  3. customdegassed
  4. temperatureAfter cooling
  5. additionthe mixture was diluted with methanol
  6. custompurified by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-e314f0692bd34631b90adca9a4a75ebc
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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