Dimethylcarbamoyl Chloride → Dimethylcarbamic acid-7-methoxy-2-(4-pyridinylamino)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl ester hydrochloride

HRID 612466Notes

Reaction equation

HRID 612466 reaction equation
Cl.[CH3:2][O:3][C:4]1[C:21]([OH:22])=[CH:20][C:7]2[CH2:8][N:9]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[CH2:10][CH2:11][CH2:12][C:6]=2[CH:5]=1.[CH3:23][N:24]([CH3:28])[C:25]([Cl:27])=[O:26].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.ClCCl>[ClH:27].[CH3:2][O:3][C:4]1[C:21]([O:22][C:25](=[O:26])[N:24]([CH3:28])[CH3:23])=[CH:20][C:7]2[CH2:8][N:9]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[CH2:10][CH2:11][CH2:12][C:6]=2[CH:5]=1

Participants

7

Reactant 4

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 19595159[7-Methoxy-8-hydroxy-1,3,4,5-tetrahydrobenzo[c]azepin-2-yl]-4-pyridinylamine hydrochloride

Product 1

HCID 70103668Dimethylcarbamic acid-7-methoxy-2-(4-pyridinylamino)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl ester hydrochlorideYield 52%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of [7-methoxy-8-hydroxy-1,3,4,5-tetrahydrobenzo[c]azepin-2-yl]-4-pyridinylamine hydrochloride 0.25 hydrate (500 mg) in chloroform (10 ml) was added dimethylcarbamyl chloride (170 μl) and triethylamine (0.75 ml). The reaction mixture was heated under reflux for 3 hrs, then cooled to room temperature, and dichloromethane (200 ml) and saturated sodium bicarbonate solution (100 ml) were added. The aqueous phase was extracted with dichloromethane (2×5 ml), the organic extracts were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was chromatographed over silica gel eluting with dichloromethane:methanol (9:1). The appropriate fractions were collected and concentrated. The residue was dissolved in methanol (5 ml), and concentrated hydrochloric acid was added. The mixture was concentrated in vacuo, and the residue was crystallized from diethyl ether-dichloromethane to give 320 mg (52%) of product, mp 95-110° C.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 3 hrs
  3. extractionThe aqueous phase was extracted with dichloromethane (2×5 ml)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was chromatographed over silica gel eluting with dichloromethane:methanol (9:1)
  8. customThe appropriate fractions were collected
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in methanol (5 ml)
  11. additionconcentrated hydrochloric acid was added
  12. concentrationThe mixture was concentrated in vacuo
  13. customthe residue was crystallized from diethyl ether-dichloromethane

Sources & evidence

ORD record
ord-8f30916688124f03ad6de74e67c2d8c9
Source dataset
uspto-grants-1999_12
Patent number
US06004977

Reaction notes

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