Hydrochloric Acid → N-Methyl-5-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)-2-pyrazinecarboxamide

HRID 222665Notes

Reaction equation

HRID 222665 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[N:6]=[CH:7][C:8]([O:11][C:12]2[CH:29]=[CH:28][C:15]3[CH2:16][CH2:17][N:18](C(OC(C)(C)C)=O)[CH2:19][CH2:20][C:14]=3[CH:13]=2)=[N:9][CH:10]=1)=[O:4].Cl.O1CCOCC1>ClCCl>[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([O:11][C:12]2[CH:29]=[CH:28][C:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][C:14]=3[CH:13]=2)=[CH:7][N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 312751,4-Dioxane2×HCID 685073281,1-Dimethylethyl 7-({5-[(methylamino)carbonyl]-2-pyrazinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

Product 1

HCID 57440291N-Methyl-5-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)-2-pyrazinecarboxamideYield 76.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 7-({5-[(methylamino)carbonyl]-2-pyrazinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (D49, Step 3) (44.26 g, 0.11 mol) in dichloromethane (800 ml) was added dropwise to a stirring solution of 4M hydrogen chloride in dioxane (270 ml, 1.1 mol). The resulting mixture was stirred at room temperature for 60 minutes. A further quantity of 4M hydrogen chloride in dioxane (30 ml, 0.12 mol) was added and the mixture stirred for 60 minutes. The resulting white solid was collected by filtration and washed with dichloromethane. The solid was dissolved in water (2 L) and basified by addition of saturated sodium carbonate solution. The water layer was extracted with dichloromethane and the extracts filtered through celite. The celite was washed with methanol and the combined dichloromethane and methanol washings were evaporated in vacuo to give the title compound (25.1 g); MS (ES+) m/e 299 [M+H]+.

Workup

  1. stirringthe mixture stirred for 60 minutes
  2. filtrationThe resulting white solid was collected by filtration
  3. washwashed with dichloromethane
  4. dissolutionThe solid was dissolved in water (2 L)
  5. additionbasified by addition of saturated sodium carbonate solution
  6. extractionThe water layer was extracted with dichloromethane
  7. filtrationthe extracts filtered through celite
  8. washThe celite was washed with methanol
  9. customthe combined dichloromethane and methanol washings were evaporated in vacuo

Sources & evidence

ORD record
ord-02dd0d14c7d14c40af69b9441a07e7b1
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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