Acetic Anhydride → N-(((1S,2S)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro [cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin]-2-yl)methyl)acetamide

HRID 1772341Notes

Reaction equation

HRID 1772341 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]3([CH2:25][C@H:24]3[CH2:26][NH2:27])[N:9]=2)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:37](OC(=O)C)(=[O:39])[CH3:38]>C(Cl)Cl>[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])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@@:10]3([CH2:25][C@H:24]3[CH2:26][NH:27][C:37](=[O:39])[CH3:38])[N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 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)methanamine2×

Product 1

HCID 57404937N-(((1S,2S)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro [cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin]-2-yl)methyl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of ((1S,2S)-4′-(4-chlorophenyl)-2′,3′,9′-trimethylspiro[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-yl)methanamine (Compound 206; 50 mg, 0.126 mmol) in DCM (2 mL) was added N,N-diisopropylethylamine (43.9 μl, 0.251 mmol). Once the reaction was cooled to 0° C., a solution of acetic anhydride in DCM (140 mg/mL) (14.23 μl, 0.151 mmol) was added. The reaction was stirred at 0° C. for 15 min before an aqueous solution of NaHCO3(sat.) was added for the quench. The product was extracted with DCM (repeated 4 times). The organic layers were combined, dried over Na2SO4 and concentrated to dryness. The residue was purified by flash chromatography (DCM/MeOH 10:0 to 9:1) to give the desired product as an off-white solid (33 mg). LRMS (M+H)+: 440 m/z. 1H NMR (two conformers detected in ˜1:1 ratio) (400 MHz, DMSO-d6) δ 8.08 (t, J=5.15 Hz, 0.5H), 7.75 (t, J=4.92 Hz, 0.5H), 7.44-7.56 (m, 4H), 3.45-3.51 (m, 1H), 2.78-2.86 (m, 0.5H), 2.64-2.72 (m, 0.5H), 2.56-2.63 (m, 3H), 2.35-2.42 (m, 3H), 2.13-2.22 (m, 0.5H), 2.00 (dd, J=5.04, 8.93 Hz, 0.5H), 1.86 (s, 1.5H), 1.71 (s, 1.5), 1.58 (m, 1.5H), 1.57 (m, 1.5H), 1.22-1.37 (m, 1H), 0.99 (dd, J=5.26, 9.16 Hz, 0.5H), 0.58 (t, J=5.95 Hz, 0.5H).

Workup

  1. additionwas added for the quench
  2. extractionThe product was extracted with DCM (repeated 4 times)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by flash chromatography (DCM/MeOH 10:0 to 9:1)

Sources & evidence

ORD record
ord-2af53cf36dfa4e47a66741f4631df81a
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

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