Water → 1,1-Dimethylethyl 4-[3-(4-amino-2,6-dimethylthieno[2,3-b]pyridin-3-yl)phenyl]-1-piperazinecarboxylate

HRID 573544Notes

Reaction equation

HRID 573544 reaction equation
Br[C:2]1[C:10]2[C:9]([NH2:11])=[CH:8][C:7]([CH3:12])=[N:6][C:5]=2[S:4][C:3]=1[CH3:13].O.CC1(C)C(C)(C)OB([C:23]2[CH:24]=[C:25]([N:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)[CH:26]=[CH:27][CH:28]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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.C(OCC)(=O)C>[NH2:11][C:9]1[CH:8]=[C:7]([CH3:12])[N:6]=[C:5]2[S:4][C:3]([CH3:13])=[C:2]([C:23]3[CH:24]=[C:25]([N:29]4[CH2:30][CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33][CH2:34]4)[CH:26]=[CH:27][CH:28]=3)[C:10]=12

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 16414220tert-Butyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylateHCID 683238623-Bromo-2,6-dimethylthieno[2,3-b]pyridin-4-amine

Product 1

HCID 683237221,1-Dimethylethyl 4-[3-(4-amino-2,6-dimethylthieno[2,3-b]pyridin-3-yl)phenyl]-1-piperazinecarboxylateYield 88.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Under nitrogen, 3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-amine (130 mg, 0.506 mmol) (Description 8) was dissolved in 1,4-dioxane (3 mL) and water (1 mL) and 1,1-dimethylethyl 4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-piperazinecarboxylate (294 mg, 0.758 mmol), tetrakis(triphenylphosphine)palladium(0) (58.4 mg, 0.051 mmol) and potassium carbonate (210 mg, 1.517 mmol) were added. The mixture was then heated in a microwave at 120° C. for 30 min. Ethyl acetate (10 mL) was added and the mixture washed with water (2×5 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo. Purification by chromatography on silica gel, eluting with a gradient of 0-70% ethyl acetate in cyclohexane, afforded the title compound (197 mg). LCMS (A) m/z: 439 [M+1]+, Rt 0.99 min (acidic).

Workup

  1. washthe mixture washed with water (2×5 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customsolvent removed in vacuo
  5. customPurification by chromatography on silica gel
  6. washeluting with a gradient of 0-70% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-b49a907f83ea4bc4a3ddb7a8aa7df69d
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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