1,2-Dichloroethane → HCID 68412346, compound

HRID 1879989Notes

Reaction equation

HRID 1879989 reaction equation
[CH2:1](Cl)[CH2:2][Cl:3].[CH3:5][NH:6][CH2:7][C:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2OC=1C.[ClH:18].[CH3:19][N:20]1[CH2:26][C:25]2[CH:27]=[C:28]([CH:31]=[CH:32][C:33]([OH:35])=O)[CH:29]=[N:30][C:24]=2[NH:23][CH2:22][CH2:21]1.Cl.CC[O:39]CC>O.C(Cl)Cl>[ClH:3].[ClH:18].[CH3:5][N:6]([CH2:7][C:8]1[O:39][C:2]2[CH:1]=[CH:14][CH:15]=[CH:16][C:11]=2[C:12]=1[CH3:13])[C:33](=[O:35])[CH:32]=[CH:31][C:28]1[CH:29]=[N:30][C:24]2[NH:23][CH2:22][CH2:21][N:20]([CH3:19])[CH2:26][C:25]=2[CH:27]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 66967084Methyl(2-methylbenzofuran-3-ylmethyl)amineHCID 68412721HCID 68412721, compound

Product 1

HCID 68412346HCID 68412346, compoundYield 53.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

EDC (0.21 g, 1.1 mmol) was added to a suspension of methyl-(2-methyl-benzofuran-3-ylmethyl)-amine (158 mg, 0.9 mmol) and 3-(4-Methyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid hydrochloride (201 mg, 0.75 mmol). The mixture was allowed to stir overnight at 40° C. The mixture was cooled to 0° C. and diluted with H2O (60 mL) with rapid stirring. The resulting precipitate was filtered, washed with H2O (20 mL) then dried under high vacuum. The solid was then subjected to flash chromatography on silica gel using 5% methonal:dichloromethane. The fractions were collected and treated with 5 mL of 2.0M HCL in Et2O. The suspension was concentrated, triturated with Et2O (50 Ml then filtered to give a coupled solid. The resulting solid was dissolved in methylene chloride (5 mL) and treated with 2M HCl in ether (0.75 mL, 1.5 mmol). The resultant yellow precipitate was filtered, triturated with diethyl ether and dried under high vacuum to afford the title compound as a white solid (186 mg, 53%) and a mixture of amide rotomers. 1H NMR (300 MHz, DMSO-d6) 11.80 (bs, 1H) 8.45-8.17 (m, 2H), 7.56-7.46 (m, 3H), 7.29-7.14 (m, 3H), 4.82-4.97 (m, 2H), 4.60-4.70 (m, 1H), 4.30-4.40 (m, 1H), 3.65-3.75 (m, 3H), 3.33-3.45 (m, 1H), 2.89-2.78 (m, 2H) 2.82 (s, 3H), 2.25 (s, 3H); MS (ESI) m/e 391 (C23H26N4O2+H)+.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. filtrationThe resulting precipitate was filtered
  3. washwashed with H2O (20 mL)
  4. customthen dried under high vacuum
  5. customThe fractions were collected
  6. additiontreated with 5 mL of 2.0M HCL in Et2O
  7. concentrationThe suspension was concentrated
  8. customtriturated with Et2O (50 Ml
  9. filtrationfiltered
  10. customto give a coupled solid
  11. filtrationThe resultant yellow precipitate was filtered
  12. customtriturated with diethyl ether
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-6259338730d9453b9208663f0174d4b5
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

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