2-Phenyl-5-tributylstannanyl-pyridine → 4-(6-((4-(Methylsulfonyl)piperazin-1-yl)methyl)-2-(6-phenylpyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine

HRID 391102Notes

Reaction equation

HRID 391102 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[S:28][C:15]3[N:16]=[C:17](SC)[N:18]=[C:19]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:14]=3[CH:13]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[C:29]1([C:35]2[CH:40]=[CH:39][C:38]([Sn](CCCC)(CCCC)CCCC)=[CH:37][N:36]=2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>COCCOC.C(OCC)(=O)C.CSC.[Cu]Br.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>[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]2[S:28][C:15]3[N:16]=[C:17]([C:38]4[CH:37]=[N:36][C:35]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)=[CH:40][CH:39]=4)[N:18]=[C:19]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:14]=3[CH:13]=2)[CH2:7][CH2:6]1)(=[O:3])=[O:4]

Participants

7

Reactant 2

HCID 146900112-Phenyl-5-tributylstannanyl-pyridineHCID 666175866-(4-Methanesulfonyl-piperazin-1-ylmethyl)-2-methylsulfanyl-4-morpholin-4-yl-thieno[2,3-d]pyrimidine

Product 1

HCID 249465344-(6-((4-(Methylsulfonyl)piperazin-1-yl)methyl)-2-(6-phenylpyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine

Reagents, catalysts & solvents 4

HCID 2724234Bromo(thiobis(methane))copperCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(4-methanesulfonyl-piperazin-1-ylmethyl)-2-methylsulfanyl-4-morpholin-4-yl-thieno[2,3-d]pyrimidine (90 mg) in 1,2-dimethoxyethane (10 mL) was added 2-phenyl-5-tributylstannanyl-pyridine (180 mg) and copper(I)bromide-dimethyl sulfide (84 mg) and the reaction mixture was stirred at room temperature for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (12 mg) was then added and the reaction mixture was heated at reflux for 16 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (20 mL) and washed with water (2×20 mL) and brine (2×20 mL). The organic phase was dried (MgSO4), reduced in vacuo and purified by column chromatography to give 387. NMR: (CDCl3): 2.65-2.69 (4 H, m), 2.82 (3 H, s, Me), 3.28-3.32 (4 H, m), 3.84 (2 H, s, CH2), 3.90-3.93 (4 H, m), 4.00-4.02 (4 H, m), 7.18 (1 H, s, Ar), 7.45-7.53 (3 H, m, Ar), 7.85 (1 H, d, J 8.5, Ar), 8.09-8.12 (2 H, m, Ar), 8.76 (1 H, d, J 8.5, Ar) and 9.72 (1 H, d, J 1.2, Ar). MS: (ESI+): MH+ 551.14

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. temperatureAfter cooling to room temperature
  4. washwashed with water (2×20 mL) and brine (2×20 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-285d2ffa317448dd993dc9651770cb81
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Reaction notes

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