Dimethylformamide → (+/-)-N-(3-pyridylmethyl)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide

HRID 727268Notes

Reaction equation

HRID 727268 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[CH:10]([CH2:24][C:25](O)=[O:26])[N:9]=2)=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN(C)C=O.[NH2:60][CH2:61][C:62]1[CH:63]=[N:64][CH:65]=[CH:66][CH:67]=1>O.C(N(CC)CC)C>[N:64]1[CH:65]=[CH:66][CH:67]=[C:62]([CH2:61][NH:60][C:25](=[O:26])[CH2:24][CH:10]2[N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]23)[CH:63]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 310183-PyridinemethanamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 197049212-[7-(4-Chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.0,2,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetic acid

Product 1

HCID 86751981(+/-)-N-(3-pyridylmethyl)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamideYield 16.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8471TriethylamineSolvent

Procedure

(±)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid (1.0 g) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (1.2 g) are added to dimethylformamide (20 ml), and the mixture is stirred. 3-(Aminomethyl)pyridine (0.30 g) and triethylamine (0.38 g) are added, and the mixture is stirred at room temperature for 6 hours. After the completion of the reaction, water (200 ml) is added and the mixture is extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is crystallized from ethyl acetate and isopropyl ether, and recrystallized from ethanol to give 200 mg of (±)-N-(3-pyridylmethyl)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide 1/2 1759 hydrate as white powdery crystals, melting point 180°-183° C.

Workup

  1. stirringthe mixture is stirred at room temperature for 6 hours
  2. additionis added
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe organic layer is washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is crystallized from ethyl acetate and isopropyl ether
  8. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-4c6e895c013d4a948a2011bf9461a519
Source dataset
uspto-grants-1998_01
Patent number
US05712274

Reaction notes

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