Sodium Hydroxide → 3-(4-amino-2-(6-(4-ethylpiperazin-1-yl)pyridin-3-ylamino)thieno[3,2-d]pyrimidin-7-yl)-N-methylbenzamide

HRID 1485491Notes

Reaction equation

HRID 1485491 reaction equation
[NH2:1][C:2]1[C:3]2[S:11][CH:10]=[C:9]([C:12]3[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=3)[C:15]([NH:17][CH3:18])=[O:16])[C:4]=2[N:5]=[C:6](Cl)[N:7]=1.[OH-].[Na+].[CH2:24]([N:26]1[CH2:31][CH2:30][N:29]([C:32]2[N:37]=[CH:36][C:35]([NH2:38])=[CH:34][CH:33]=2)[CH2:28][CH2:27]1)[CH3:25].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.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]>[NH2:1][C:2]1[C:3]2[S:11][CH:10]=[C:9]([C:12]3[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=3)[C:15]([NH:17][CH3:18])=[O:16])[C:4]=2[N:5]=[C:6]([NH:38][C:35]2[CH:36]=[N:37][C:32]([N:29]3[CH2:30][CH2:31][N:26]([CH2:24][CH3:25])[CH2:27][CH2:28]3)=[CH:33][CH:34]=2)[N:7]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 91616746-(4-Ethylpiperazin-1-yl)pyridin-3-amineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866756523-(4-amino-2-chlorothieno[3,2-d]pyrimidin-7-yl)-N-methylbenzamide

Product 1

HCID 532374933-(4-amino-2-(6-(4-ethylpiperazin-1-yl)pyridin-3-ylamino)thieno[3,2-d]pyrimidin-7-yl)-N-methylbenzamideYield 55.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

3-(4-Amino-2-chlorothieno[3,2-d]pyrimidin-7-yl)-N-methylbenzamide (20 mg, 0.063 mmol) was dissolved in dioxane (1 mL) and then sodium hydroxide (13 mg, 0.31 mmol) and 6-(4-ethylpiperazin-1-yl)pyridin-3-amine (19 mg, 0.094 mmol) were added. After flowing nitrogen gas to the reaction mixture for 10 minutes, Pd2(dba)3 (4 mg, 0.004 mmol) and X-phos (1 mg, 0.12 mmol) were added. The reaction mixture was stirred at 120° C. for 2 hours and filtered with celite. The filtrate was diluted with ethyl acetate and then washed with brine. The organic layer was dried with magnesium sulfate, filtered with celite, and then concentrated. Purification by chromatography (5% methanol/dichloromethane) yielded the target compound (17 mg, 55% yield) of Example 1.

Workup

  1. customfor 10 minutes
  2. filtrationfiltered with celite
  3. additionThe filtrate was diluted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered with celite
  7. concentrationconcentrated
  8. customPurification by chromatography (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-3b57ab10dbb84babb69aa893f9454485
Source dataset
uspto-grants-2016_08
Patent number
US09422307B2

Reaction notes

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