p-Toluenesulfonic acid monohydrate → HCID 44473400, compound

HRID 2362614Notes

Reaction equation

HRID 2362614 reaction equation
C(O[CH:4](OCC)[CH2:5][C:6]1[N:10]=[N:9][N:8]([CH:11]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[CH:18][C:17]([O:23][CH2:24][CH2:25][O:26][CH3:27])=[CH:16]3)[CH3:12])[C:7]=1[C:28]([NH:30][C:31]1[S:35][N:34]=[C:33]([CH3:36])[CH:32]=1)=[O:29])C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClC(Cl)C.ClCCl>[CH3:27][O:26][CH2:25][CH2:24][O:23][C:17]1[CH:18]=[N:19][C:20]2[C:15]([CH:16]=1)=[CH:14][C:13]([C@@H:11]([N:8]1[C:7]3[C:28](=[O:29])[N:30]([C:31]4[S:35][N:34]=[C:33]([CH3:36])[CH:32]=4)[CH:4]=[CH:5][C:6]=3[N:10]=[N:9]1)[CH3:12])=[CH:22][CH:21]=2

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 58270296HCID 58270296, compound

Product 1

HCID 44473400HCID 44473400, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
100 °C

Procedure

5-(2,2-diethoxyethyl)-3-(1-(3-(2-methoxyethoxy)quinolin-6-yl)ethyl)-N-(3-methylisothiazol-5-yl)-3H-1,2,3-triazole-4-carboxamide (0.296 g, 0.53 mmol) was dissolved in dichloroethane (5 mL) and to the solution was added p-toluenesulfonic acid monohydrate (0.11 g, 0.59 mmol). The reaction mixture was heated at 100° C. overnight. The reaction mixture was diluted with dichloromethane then washed with sat. aq. sodium bicarbonate and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The enantiomers were separated via preparative SFC (ChiralPak® AD-H, 20×250 mm, 40:60:0.2 IPA:CO2:DEA, 80 mL/min; tr 1.38 min) to yield (S)-3-(1-(3-(2-methoxyethoxy)quinolin-6-yl)ethyl)-5-(3-methylisothiazol-5-yl)-3H-[1,2,3]triazolo[4,5-c]pyridin-4(5H)-one as a pale yellow solid. On the basis of previous crystallographic data and potency recorded for related compounds in the same program, the absolute stereochemistry was assigned as the S enantiomer. MS m/z=463.2 [M+1]+. Calc'd 462.5 for C23H22N6O3S. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.15 (d, 3 H) 2.39-2.44 (m, 3 H) 3.30-3.32 (m, 3 H) 3.71 (dd, 2 H) 4.23 (dd, 2 H) 6.89 (q, 1 H) 7.33 (d, 1 H) 7.64 (dd, 1 H) 7.74-7.82 (m, 3 H) 7.94 (d, 1 H) 8.34 (d, 1 H) 8.61 (d, 1 H).

Workup

  1. washthen washed with sat. aq. sodium bicarbonate and brine
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe enantiomers were separated via preparative SFC (ChiralPak® AD-H, 20×250 mm, 40:60:0.2 IPA:CO2:DEA, 80 mL/min; tr 1.38 min)

Sources & evidence

ORD record
ord-a3184c873586425086913e2e4642d72c
Source dataset
uspto-grants-2014_04
Patent number
US08691838B2

Reaction notes

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