Thioglycolic Acid → HCID 136348413, compound

HRID 1748715Notes

Reaction equation

HRID 1748715 reaction equation
ClC1C=CC([CH:8]2[S:14][CH2:13][CH2:12][NH:11][C:10]3[N:15](C)[N:16]=[C:17](C4N(CC5C=CC(OC)=CC=5)N=CC=4)[C:9]2=3)=C(C)C=1.COC1C=CC(CN2C(C(OCC)=O)=CC=N2)=CC=1.CNN.C(O)(=O)CS.ClC1C=CC(C=O)=C(C)C=1.FC(F)(F)C(O)=O.[OH-].[Na+]>>[NH:15]1[C:10]2[NH:11][CH2:12][CH2:13][S:14][CH2:8][C:9]=2[CH:17]=[N:16]1

Participants

8

Reactant 7

HCID 1133Thioglycolic AcidHCID 6061MethylhydrazineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 27576584-Chloro-2-methylbenzaldehydeHCID 54208979ethyl 1-(4-methoxybenzyl)-1H-pyrazole-5-carboxylateHCID 136348414HCID 136348414, compound

Product 1

HCID 136348413HCID 136348413, compoundYield 63%

Conditions

Temperature
140 °C

Procedure

To 4-(4-chloro-2-methyl-phenyl)-3-[2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-1-methyl-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.32 g, 0.67 mmol, prepared using A with ethyl 1-(4-methoxybenzyl)-1H-pyrazole-5-carboxylate (WO2011079076), B with methylhydrazine, C with thioglycolic acid and 4-chloro-2-methylbenzaldehyde (Fluorochem) and D) was added trifluoroacetic acid (5 mL). The resulting mixture was heated, in a sealed microwave vessel, for about 10 min, at about 140° C., in a microwave. After cooling to rt the mixture was made basic (pH ˜8) with 2 M aqueous NaOH and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate) to give 4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(1H-pyrazol-3 or 5-yl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.151 g, 0.42 mmol, 63%) as an off white solid: LC-MS (Table 1, Method e) Rt=2.83 min, m/z 360 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) 2.54 (3H, s) 2.64-2.72 (1H, m) 2.77-2.86 (1H, m) 3.21-3.31 (1H, m) 3.54-3.63 (1H, m) 3.77-3.83 (1H, br s) 3.81 (3H, s) 5.69 (1H, br. S.) 6.18 (1H, br s) 7.04 (1H, dd, J=8.5, 2.0 Hz) 7.08 (1H, d, J=8.5 Hz) 7.20 (1H, br s) 7.47 (1H, d, J=2.0 Hz) 10.1 (1H, br s).

Workup

  1. temperatureAfter cooling to rt the mixture
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (SiO2, ethyl acetate)

Sources & evidence

ORD record
ord-6429628a62874c31a16f53b99ff303c6
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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