Ethylamine hydrochloride → 2-[(4S)-6-(4-chlorophenyl)-8-hydroxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide

HRID 513166Notes

Reaction equation

HRID 513166 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([OH:19])[CH:17]=[CH:18][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@H:10]([CH2:24][C:25](O)=[O:26])[N:9]=2)=[CH:4][CH:3]=1.Cl.[CH2:29]([NH2:31])[CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([OH:19])[CH:17]=[CH:18][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@H:10]([CH2:24][C:25]([NH:31][CH2:29][CH3:30])=[O:26])[N:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 11198Ethylamine hydrochloride2×HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68003932[(4S)-6-(4-chlorophenyl)-8-hydroxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetic acid

Product 1

HCID 529354812-[(4S)-6-(4-chlorophenyl)-8-hydroxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamideYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Intermediate 22 (383 mg, 1.00 mmol), ethylamine hydrochloride (163 mg, 2.0 mmol), HATU (457 mg, 1.20 mmol) and DIPEA (0.349 mL, 2.0 mmol) were dissolved in DMF (2 mL) and stirred at RT overnight. More ethylamine hydrochloride (163 mg, 2.0 mmol) and DIPEA (0.349 mL, 2.0 mmol) were added and the reaction stirred for a further 2 h. The reaction mixture was diluted with EtOAc (20 mL) and washed with saturated aqueous sodium bicarbonate solution (10 mL), water and brine. The organic phase was dried and evaporated under vacuum. Purification of the residue by flash chromatography on silica gel (DCM-methanol 10 to 20% gradient) gave the title compound as an off-white solid (200 mg, 0.488 mmol, 49% yield). LC/MS (M(35Cl)+H)+ 410, (M(37Cl)+H)+ 412; RT 0.76 min (using LC/MS apparatus c)).

Workup

  1. stirringthe reaction stirred for a further 2 h
  2. washwashed with saturated aqueous sodium bicarbonate solution (10 mL), water and brine
  3. customThe organic phase was dried
  4. customevaporated under vacuum
  5. customPurification of the residue by flash chromatography on silica gel (DCM-methanol 10 to 20% gradient)

Sources & evidence

ORD record
ord-d0e836d0256048e9b92a5989fbdb70d8
Source dataset
uspto-grants-2015_08
Patent number
US09102677B2

Reaction notes

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