Potassium Carbonate → N2-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-N4-cyclopropylfuro[3,2-d]pyrimidine-2,4-diamine

HRID 1038805Notes

Reaction equation

HRID 1038805 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][CH:12]2[CH2:14][CH2:13]2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[N:23]1[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]1)[NH2:19].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(O)(C)C>[Cl:15][C:16]1[CH:17]=[C:18]([NH:19][C:2]2[N:3]=[C:4]([NH:11][CH:12]3[CH2:14][CH2:13]3)[C:5]3[O:10][CH:9]=[CH:8][C:6]=3[N:7]=2)[CH:20]=[CH:21][C:22]=1[N:23]1[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 8203433-Chloro-4-(4-methylpiperazin-1-yl)anilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866650932-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine

Product 1

HCID 67129973N2-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-N4-cyclopropylfuro[3,2-d]pyrimidine-2,4-diamineYield 43.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
85 °C

Procedure

To a vial was added 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.099 g, 0.476 mmol, Preparation #A.1), 3-chloro-4-(4-methylpiperazin-1-yl)aniline (0.118 g, 0.523 mmol, Art-Chem), X-Phos (0.0136 g, 0.029 mmol), K2CO3 (0.079 g, 0.571 mmol), and Pd2dba3 (0.026 g, 0.029 mmol). t-BuOH (2 mL) was then added and tube was sealed. The tube was evacuated and purged with nitrogen (3×), and stirred overnight at about 85° C. The mixture was filtered, the filter pad was washed with EtOAc and then the solvent was removed in vacuo. The crude material was added to a silica gel column and was eluted with MeOH/DCM (2% to 10%). The sample was further purified by preparative reverse phase HPLC (Table 2, Method b). The collected fractions were dissolved in DCM (10 mL) and washed with saturated aqueous NaHCO3, (10 mL) and separated using a Biotage phase separator column. The filtrate was concentrated to provide N2-(3-chloro-4-(4-methylpiperazin-1-yl)phenyl)-N4-cyclopropylfuro[3,2-d]pyrimidine-2,4-diamine (0.082 g, 43%): LC/MS (Table 2, Method a) Rt=1.04 min; MS m/z 399.2 (M+H)+. Syk IC50=B

Workup

  1. customtube was sealed
  2. customThe tube was evacuated
  3. custompurged with nitrogen (3×)
  4. filtrationThe mixture was filtered
  5. washthe filter pad was washed with EtOAc
  6. customthe solvent was removed in vacuo
  7. additionThe crude material was added to a silica gel column
  8. washwas eluted with MeOH/DCM (2% to 10%)
  9. customThe sample was further purified by preparative reverse phase HPLC (Table 2, Method b)
  10. dissolutionThe collected fractions were dissolved in DCM (10 mL)
  11. washwashed with saturated aqueous NaHCO3, (10 mL)
  12. customseparated
  13. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-9c79c298687343adb4ccb9b914b32f9b
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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