2-Methoxyaniline → HCID 178470157, compound

HRID 727260Notes

Reaction equation

HRID 727260 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[C:10]([C:28]([O:30][CH2:31][CH3:32])=[O:29])(CC(O)=O)[N:9]=2)=[CH:4][CH:3]=1.[OH:33]N1C2C=CC=CC=2N=N1.Cl.CN(CCCN=C=N[CH2:53][CH3:54])C.[CH3:55][O:56][C:57]1[CH:63]=[CH:62][CH:61]=[CH:60][C:58]=1[NH2:59]>CN(C)C=O.O.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[SH:17]([CH:54]=[C:53]=[O:33])[C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C:10]([NH:59][C:58]3[CH:60]=[CH:61][CH:62]=[CH:63][C:57]=3[O:56][CH3:55])([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 70002-MethoxyanilineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 197049582-(4-(4-Chlorophenyl)-6-(ethoxycarbonyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid

Product 1

HCID 178470157HCID 178470157, compoundYield 63.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

(±)-4-(4-Chlorophenyl)-6-ethoxycarbonyl-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid (2.0 g) is dissolved in dimethylformamide (20 ml). 1-Hydroxybenzotriazole (HOBt, 0.81 g), N-dimethylaminopropyl-N'-ethylcarbodiimide hydrochloride (WSC, 1.10 g) and triethyl amine (0.77 ml) are added in order under ice-cooling, and the mixture is stirred. Ten minutes later, a solution of 2-methoxyaniline (0.65 g) dissolved in dimethylformamide (6 ml) is dropwise added to the reaction mixture, and the mixture is stirred at room temperature overnight. The reaction mixture is poured into water and extracted with toluene. The organic layer is washed with a 10% aqueous solution of hydrochloric acid, an aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous magnesium sulfate. After removing the solvent, the residue is recrystallized from ethanol to give 1.55 g of (±)-ethyl 4-(4-chlorophenyl)-6-(2-methoxyanilino)-carbonylmethyl-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4, 3-a][1,4]diazepine-6-carboxylate. 1/2 hydrate, melting point 136°-138° C.

Workup

  1. temperaturecooling
  2. additionis dropwise added to the reaction mixture
  3. stirringthe mixture is stirred at room temperature overnight
  4. extractionextracted with toluene
  5. washThe organic layer is washed with a 10% aqueous solution of hydrochloric acid
  6. dry with materialan aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous magnesium sulfate
  7. customAfter removing the solvent
  8. customthe residue is recrystallized from ethanol

Sources & evidence

ORD record
ord-7c70d19c26404c28be4891b02f5703ba
Source dataset
uspto-grants-1998_01
Patent number
US05712274

Reaction notes

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