Stannane, tributyl(1-ethoxyethenyl)- → 2-Acetyl-5-[2-(4-Cyclobutylpiperazin-1-Yl)-2-Oxoethyl]-4,5,6,7-Tetrahydro[1,3]Thiazolo[5,4-C]Pyridine

HRID 1713155Notes

Reaction equation

HRID 1713155 reaction equation
Br[C:2]1[S:3][C:4]2[CH2:5][N:6]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:23][CH2:22][CH2:21]4)[CH2:16][CH2:15]3)=[O:13])[CH2:7][CH2:8][C:9]=2[N:10]=1.C([Sn](CCCC)(CCCC)[C:29]([O:31]CC)=[CH2:30])CCC>C1(C)C=CC=CC=1.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:29]([C:2]1[S:3][C:4]2[CH2:5][N:6]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:23][CH2:22][CH2:21]4)[CH2:16][CH2:15]3)=[O:13])[CH2:7][CH2:8][C:9]=2[N:10]=1)(=[O:31])[CH3:30]

Participants

5

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 574205862-Bromo-5-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine

Product 1

HCID 574206292-Acetyl-5-[2-(4-Cyclobutylpiperazin-1-Yl)-2-Oxoethyl]-4,5,6,7-Tetrahydro[1,3]Thiazolo[5,4-C]Pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-bromo-5-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine (300 mg, 0.75 mmol), tributyl(1-ethoxy-vinyl)tin (361 mg, 1 mmol) and Pd(PPh3)4 (92 mg, 0.08 mmol) in toluene (15 mL) is degassed with argon and heated at 110° C. in a sealed tube overnight. The mixture is cooled and saturated KF solution (10 mL) is added. The mixture is stirred at rt for 30 min, and then the layers are separated. The aqueous layer is extracted with EtOAc (15 ml) and the combined extracts are dried and evaporated. The residue is dissolved in THF (10 mL), 2N HCl (10 mL) is added and the mixture is stirred at rt for 30 min. Solid Na2CO3 is added until pH>7 and the layers are separated. The aqueous layer is extracted with EtOAc (15 ml) and the combined extracts are dried and evaporated. The residue is purified by PTLC to give the title compound as a white solid. MS (M+1): 363.0; 1H NMR (δ, CDCl3): 3.88 (s, 2H), 3.52-3.62 (m, 4H), 3.41 (s, 2H), 2.99 (s, 4H), 2.62-2.77 (m, 4H), 2.29 (q, 4H), 1.66-2.08 (m, 6H).

Workup

  1. customis degassed with argon
  2. temperatureThe mixture is cooled
  3. additionsaturated KF solution (10 mL) is added
  4. customthe layers are separated
  5. extractionThe aqueous layer is extracted with EtOAc (15 ml)
  6. customthe combined extracts are dried
  7. customevaporated
  8. dissolutionThe residue is dissolved in THF (10 mL)
  9. addition2N HCl (10 mL) is added
  10. stirringthe mixture is stirred at rt for 30 min
  11. additionSolid Na2CO3 is added until pH>7
  12. customthe layers are separated
  13. extractionThe aqueous layer is extracted with EtOAc (15 ml)
  14. customthe combined extracts are dried
  15. customevaporated
  16. customThe residue is purified by PTLC

Sources & evidence

ORD record
ord-9922cfaed0644eb484b0c28ac5819a62
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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