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 1711843Notes

Reaction equation

HRID 1711843 reaction equation
C([O:5][C:6](=[O:31])/[CH:7]=[CH:8]/[C:9]1[CH:30]=[N:29][C:12]2[NH:13][C:14](=[O:28])[CH2:15][N:16]([CH2:18][C:19]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[O:20])[CH2:17][C:11]=2[CH:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:40]>>[ClH:40].[CH3:27][N:24]1[CH2:23][CH2:22][N:21]([C:19](=[O:20])[CH2:18][N:16]2[CH2:17][C:11]3[CH:10]=[C:9](/[CH:8]=[CH:7]/[C:6]([OH:31])=[O:5])[CH:30]=[N:29][C:12]=3[NH:13][C:14](=[O:28])[CH2:15]2)[CH2:26][CH2:25]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59456905(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 tert-butyl ester

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 hydrochloride

Procedure

A suspension of (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 tert-butyl ester (1.12 g, 2.61 mmol) in CH2Cl2 (10 mL) was treated with TFA (10 mL). After stirring at room temperature for 35 min, the solution was concentrated in vacuo. The resulting oil was treated with anhydrous HCl (20 mL of a 4.0 M solution in dioxane, 80 mmol) and the resulting mixture was sonicated for 1 h. The mixture was diluted with Et2O (50 mL) and sonicated for 10 min. The solid was isolated by filtration, washed with Et2O and dried under vacuum at 50° C. for 4 h to give the title compound (1.72 g, quantitative) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 11.60 (br s, 1H), 11.09 (br s, 1H), 8.82 (s, 1H), 8.47 (s, 1H), 7.66 (d, J=19.9 Hz, 1H), 6.65 (d, J=16.1 Hz, 1H), 4.43-4.40 (m, 2H), 4.31 (br s, 2H), 3.95-3.91 (m, 1H), 3.84 (br s, 2H), 3.56 (s, 4H), 3.42 (br s, 2H), 3.23-2.97 (m, 2H), 2.76 (d, J=4.1 Hz, 3H); MS (ESI) m/e 374 (M+H)+.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. additionThe resulting oil was treated with anhydrous HCl (20 mL of a 4.0 M solution in dioxane, 80 mmol) and the resulting mixture
  3. customwas sonicated for 1 h
  4. additionThe mixture was diluted with Et2O (50 mL)
  5. customsonicated for 10 min
  6. customThe solid was isolated by filtration
  7. washwashed with Et2O
  8. customdried under vacuum at 50° C. for 4 h

Sources & evidence

ORD record
ord-2f1bb46b3a5f44e1a2159508213412ff
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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