Trifluoroacetic acid → HCID 136348427, compound

HRID 1748742Notes

Reaction equation

HRID 1748742 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][CH2:13][NH:12][C:11]2[N:16]([CH3:31])[N:17]=[C:18]([C@@H:19]3[CH2:23][CH2:22][CH2:21][N:20]3C(OC(C)(C)C)=O)[C:10]1=2.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][CH2:13][NH:12][C:11]2[N:16]([CH3:31])[N:17]=[C:18]([C@@H:19]3[CH2:23][CH2:22][CH2:21][NH:20]3)[C:10]1=2

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 136348426HCID 136348426, compound

Product 1

HCID 136348427HCID 136348427, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To tert-butyl (2S)-2-[4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-3-yl]pyrrolidine-1-carboxylate (0.31 g, 0.64 mmol), was added trifluoroacetic acid in DCM (1:4, 20 mL). The resulting mixture was stirred, for about 18 h, at rt. Subsequently, 5% aqueous sodium bicarbonate (100 mL) and DCM (200 mL) were added. The layers were separated and the organic layer was washed with water (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate/methanol (9:1) followed by 10% methanol in DCM) to afford 4-(2,4-dichlorophenyl)-1-methyl-3-[(2S)-pyrrolidin-2-yl]-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (38 mg, 0.1 mmol, 32%), as white solid: LC-MS (Table 1, Method a) Rt=1.38 min, m/z 383 (M+H)+; Major diastereomer; 1H NMR (400 MHz, CDCl3 and two drops of TFA) δ ppm 1.22-1.28 (1H, m) 1.85-2.35 (3H, m) 2.50-2.60 (1H, m) 2.68-2.83 (2H, m) 3.35-3.65 (3H, m) 3.75-3.85 (1H, m) 3.87 (3H, s) 4.60-4.70 (1H, br s) 5.32 (1H, s) 6.97 (1H, d, J=8.0 Hz) 7.16 (1H, dd, J=8.3, 2.2 Hz) 7.47 (1H, d, J=2.1 Hz) 9.65 (1H, br s). Minor diastereomer; 1H NMR (400 MHz, CDCl3 and two drops of TFA) δ ppm 1.22-1.28 (1H, m) 1.85-2.35 (4H, m) 2.68-2.83 (2H, m) 3.35-3.65 (3H, m) 3.75-3.85 (1H, m) 3.87 (3H, s) 4.60-4.70 (1H, br s) 5.31 (1H, s) 6.95 (1H, d, J=8.0 Hz) 7.10 (1H, dd, J=8.3, 2.2 Hz) 7.43 (1H, d, J=2.1 Hz) 9.25 (1H, br s).

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with water (25 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (SiO2, ethyl acetate/methanol (9:1) followed by 10% methanol in DCM)

Sources & evidence

ORD record
ord-0b1b28eb954d4e39bfc93dcdcb0f78e5
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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