Dichloromethane → (E)-3-{4-[2-(4-Methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl}acrylic acid hydrochloride

HRID 1711842Notes

Reaction equation

HRID 1711842 reaction equation
Br[C:2]1[CH:23]=[N:22][C:5]2[NH:6][C:7](=[O:21])[CH2:8][N:9]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]3)=[O:13])[CH2:10][C:4]=2[CH:3]=1.[C:24]([O:28]C(C)(C)C)(=[O:27])[CH:25]=[CH2:26].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(Cl)[Cl:65]>C(#N)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[ClH:65].[CH3:20][N:17]1[CH2:18][CH2:19][N:14]([C:12](=[O:13])[CH2:11][N:9]2[CH2:10][C:4]3[CH:3]=[C:2](/[CH:26]=[CH:25]/[C:24]([OH:28])=[O:27])[CH:23]=[N:22][C:5]=3[NH:6][C:7](=[O:21])[CH2:8]2)[CH2:15][CH2:16]1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 594569067-Bromo-4-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 66967110(E)-3-{4-[2-(4-Methyl-piperazin-1-yl)-2-oxo-ethyl]-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl}acrylic acid hydrochlorideYield 72%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A suspension of 7-Bromo-4-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (1.39 g, 3.64 mmol) in propionitrile (32 mL) and DMF (8 mL) was de-oxygenated with Ar for 15 min. The mixture was treated with tert-butyl acrylate (2.1 mL, 14 mmol) and (i-Pr)2EtN (1.3 mL, 7.4 mmol) and then was de-oxygenated with Ar for 10 min. Pd(OAc)2 (83 mg, 0.37 mmol) and P(o-tol)3 (0.22 g, 0.73 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 10 min. The mixture was heated to reflux overnight, then allowed to cool. The resulting precipitate was isolated by filtration and dissolved in CH2Cl2. The solution was filtered through Celite and the solvent was removed in vacuo to give the title compound (1.13 g, 72%) as an off-white solid: MS (ESI) m/e 430 (M+H)+.

Workup

  1. waitwas de-oxygenated with Ar for 10 min
  2. customfor 10 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. customThe resulting precipitate was isolated by filtration
  7. filtrationThe solution was filtered through Celite
  8. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-88720258b9354494b852440be1d03834
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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