Dimethylformamide → 2-Cyano-5-[2-(4-Cyclobutylpiperazin-1-Yl)-2-Oxoethyl]-4,5,6,7-Tetrahydro[1,3]Thiazolo[5,4-C]Pyridine

HRID 1713156Notes

Reaction equation

HRID 1713156 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.[CH3:24][N:25](C=O)C>[C-]#N.[C-]#N.[Zn+2].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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:24]([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)#[N:25]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 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 594635712-Cyano-5-[2-(4-Cyclobutylpiperazin-1-Yl)-2-Oxoethyl]-4,5,6,7-Tetrahydro[1,3]Thiazolo[5,4-C]Pyridine

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

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 (40 mg, 0.1 mmol), Zn(CN)2 (15 mg, 0.2 mmol), Pd2(dba)3 (5 mg, 0.005 mmol) and dppf (6 mg, 0.01 mmol) in DMF (4 mL) is degassed with argon and heated at 110° C. in a sealed tube overnight. The mixture is cooled and solvent is removed in vacuo. The residue is partitioned between water (3 mL) and EtOAc (3 mL). The aqueous layer is extracted with EtOAc (4 ml) and the combined extracts are dried and evaporated. The residue is purified by PTLC to give the title compound as a light yellow solid. MS (M+1): 346.0; 1H NMR (δ, CDCl3): 3.92 (s, 2H), 3.55-3.67 (m, 4H), 3.45 (s, 2H), 3.00 (s, 4H), 2.66-2.77 (m, 1H), 2.31 (s, 4H), 1.63-2.08 (m, 6H).

Workup

  1. customis degassed with argon
  2. temperatureThe mixture is cooled
  3. customsolvent is removed in vacuo
  4. customThe residue is partitioned between water (3 mL) and EtOAc (3 mL)
  5. extractionThe aqueous layer is extracted with EtOAc (4 ml)
  6. customthe combined extracts are dried
  7. customevaporated
  8. customThe residue is purified by PTLC

Sources & evidence

ORD record
ord-cee3e4aa06aa49b5816dad9a3e93ca65
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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