Water → HCID 136348420, compound

HRID 1748718Notes

Reaction equation

HRID 1748718 reaction equation
Cl.Cl.[CH3:3][N:4]1[C:8]2[NH:9][CH2:10][CH2:11][S:12][CH:13]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:7]=2[C:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)=[N:5]1.C(N(CC)C(C)C)(C)C.[C:35](Cl)(=[O:37])[CH3:36].O>C(Cl)Cl>[CH3:3][N:4]1[C:8]2[NH:9][CH2:10][CH2:11][S:12][CH:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:35](=[O:37])[CH3:36])[CH2:16][CH2:15]3)[C:7]=2[C:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)=[N:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 136348417HCID 136348417, compound

Product 1

HCID 136348420HCID 136348420, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-10 °C

Procedure

To a mixture of 1-methyl-4-(4-piperidyl)-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine dihydrochloride (0.10 g, 0.25 mmol) and N,N-diisopropylethylamine (0.14 mL, 0.8 mmol) in DCM (20 mL) was added dropwise a solution of acetyl chloride (0.018 mL, 0.25 mmol) in DCM (2 mL), at about −10° C. The resulting mixture was stirred at about −10° C. for about 2 h and about 1 h at rt, then water (10 mL) and DCM (20 mL) were added. The layers were separated and the organic layer was washed with water (10 mL) and brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, DCM/methanol 95:5) to give 1-[4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]-1-piperidyl]ethanone (0.090 g, 97%) as a white solid: LC-MS (Table 1, Method a) Rt=1.60 min; m/z 372 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) (The spectrum is described as a 1:1 mixture of two compounds (‘rotamers’), each contributing 25 protons) δ 1.11 (1H, td, J=12.4, 4.3 Hz) 1.17-1.37 (4H, m) 1.38-1.50 (2H, m) 2.01 (3H, s) 2.07 (3H, s) 2.08-2.28 (4H, m) 2.39 (1H, td, J=12.7, 2.9 Hz) 2.65-2.74 (2H, m) 2.86 (1H, td, J=12.8, 2.9 Hz) 2.96-3.13 (5H, m) 3.39-3.54 (4H, m) 3.65 (1H, br. d, J=13.6 Hz) 3.77 (3H, s) 3.78 (3H, s) 3.84 (1H, br. d, J=13.6 Hz) 4.40 (1H, br. d, J=13.5 Hz) 4.63 (1H, br. d, J=13.7 Hz) 5.04 (1H, d, J=9.5 Hz) 5.06 (1H, d, J=9.9 Hz) 7.11-7.17 (2H, m) 7.63-7.69 (2H, m) 7.84-7.92 (2H, m) 8.50-8.56 (2H, m).

Workup

  1. customat about −10° C
  2. customThe layers were separated
  3. washthe organic layer was washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2, DCM/methanol 95:5)

Sources & evidence

ORD record
ord-8817452a66f44aa09f7200593d27f2bc
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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