Ammonium Hydroxide → ((1S,2S)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro[cyclo-propane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin]-2-yl)methanamine

HRID 1772340Notes

Reaction equation

HRID 1772340 reaction equation
Br[CH2:2][C@H:3]1[C@@:5]2([N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)[C:9]3[C:19]([CH3:23])=[C:20]([CH3:22])[S:21][C:8]=3[N:7]3[C:24]([CH3:27])=[N:25][N:26]=[C:6]23)[CH2:4]1.[OH-].[NH4+:29]>CN(C=O)C>[Cl:18][C:15]1[CH:14]=[CH:13][C:12]([C:10]2[C:9]3[C:19]([CH3:23])=[C:20]([CH3:22])[S:21][C:8]=3[N:7]3[C:24]([CH3:27])=[N:25][N:26]=[C:6]3[C@@:5]3([CH2:4][C@H:3]3[CH2:2][NH2:29])[N:11]=2)=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 14923Ammonium HydroxideHCID 57404762(1S,2R)-2-(bromomethyl)-4'-(4-chlorophenyl)-2',3',9'-trimethylspiro-[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]

Product 1

HCID 57404936((1S,2S)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro[cyclo-propane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin]-2-yl)methanamineYield 4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (1S,2R)-2-(bromomethyl)-4′-(4-chlorophenyl)-2′,3′,9′-trimethylspiro-[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine](350 mg, 0.758 mmol) in DMF (4 mL) was added ammonium hydroxide (3 mL, 77 mmol) at rt. After 9 h at rt, silica gel was added, and the solvent was removed under vacuum. The dry silica gel was packed, and the product was purified by chromatography (Hexane/EtOAc 5:5 to 0:10 then DCM/MeOH 10:0 to 9:1). A second (EtOAc/toluene/MeOH 4:4:2) and a third chromatography were performed (2-propanol 100%) to give a tan solid (12 mg). LRMS (M+H)+: 398 m/z.

Workup

  1. additionsilica gel was added
  2. customthe solvent was removed under vacuum
  3. customthe product was purified by chromatography (Hexane/EtOAc 5:5 to 0:10

Sources & evidence

ORD record
ord-a1024bc598564ee2bd566a1b2e723279
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

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