1,2-Dichloroethane → 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

HRID 1362083Notes

Reaction equation

HRID 1362083 reaction equation
Cl.[Br:2][C:3]1[CH:18]=[N:17][C:6]2[NH:7][C:8](=[O:16])[CH2:9][N:10]([CH2:12][C:13]([OH:15])=O)[CH2:11][C:5]=2[CH:4]=1.C(N(C(C)C)C(C)C)C.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl>[Br:2][C:3]1[CH:18]=[N:17][C:6]2[NH:7][C:8](=[O:16])[CH2:9][N:10]([CH2:12][C:13]([N:32]3[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]3)=[O:15])[CH2:11][C:5]=2[CH:4]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66967063(7-Bromo-2-oxo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-4-yl)acetic acid hydrochloride

Product 1

HCID 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-oneYield 83.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of (7-bromo-2-oxo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-4-yl)acetic acid hydrochloride (1.66 g, 4.45 mmol) in CH2Cl2 (50 mL) was treated sequentially with (i-Pr)2EtN (3.1 mL, 18 mmol), N-methyl piperazine (0.54 mL, 4.87 mmol), HOBt (0.66 g, 4.88 mmol), and EDC (0.95 g, 4.96 mmol). After stirring overnight, the mixture was diluted with CH2Cl2 (100 mL) and then washed with H2O (100 mL). The aqueous layer was extracted with CH2Cl2 (4×100 mL). The combined organic layers were dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 95:5) gave the title compound (1.42 g, 83%) as an off-white solid: MS (ESI) m/e 382 (M+H)+.

Workup

  1. washwashed with H2O (100 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (4×100 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo
  6. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 95:5)

Sources & evidence

ORD record
ord-74bd26b00ec64d7a885ae6cedf1fcd61
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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