p-Toluenesulfonyl isocyanate → HCID 90047713, compound

HRID 1754261Notes

Reaction equation

HRID 1754261 reaction equation
[C:1]1([C:7]2[CH:20]=[CH:19][C:10]3[N:11]=[C:12]([CH2:14][C:15]([NH:17][NH2:18])=[O:16])[S:13][C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:21]1([CH3:33])[CH:26]=[CH:25][C:24]([S:27]([N:30]=[C:31]=O)(=[O:29])=[O:28])=[CH:23][CH:22]=1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>O1CCOCC1.CO>[CH3:33][C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:30][C:31]2[O:16][C:15]([CH2:14][C:12]3[S:13][C:9]4[CH:8]=[C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[CH:20]=[CH:19][C:10]=4[N:11]=3)=[N:17][N:18]=2)(=[O:29])=[O:28])=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 77703p-Toluenesulfonyl isocyanateHCID 111923Propylphosphonic anhydrideHCID 58470188HCID 58470188, compound

Product 1

HCID 90047713HCID 90047713, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 2-(6-phenylbenzo[d]thiazol-2-yl)acetohydrazide (26 mg, 0.092 mmol) (described in WO 2011/074560) in dioxane (0.8 mL) was added p-toluenesulfonyl isocyanate (15 μL, 0.10 mmol), and the reaction mixture stirred for 15 min. 1-Propanephosphonic acid cyclic anhydride (50% in EtOAc) (0.164 mL, 0.275 mmol) was added and the reaction mixture stirred at 105° C. for 18 h. The reaction mixture was allowed to cool to rt, diluted with MeOH then purified by preparative HPLC (RT=8.79 min using Axia Luna 5 u C18 30×100 mm column with flow rate of 40 mL/min over 10 min period. Solvent A=10/90/0.1% ACN/H2O/TFA, Solvent B=90/10/0.1%, 10 to 100% B). The fraction containing product was evaporated to dryness and the residue chromatographed on silica gel eluting with 0 to 10% MeOH/DCM to give Compound 90a (5 mg, 12%) as a white solid. LCMS=1.01 min using analytical method (M), 462.9 (M+H). 1H NMR (400 MHz, CDCl3, 60° C.) δ 8.08-7.99 (m, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.70 (d, J=8.5 Hz, 1H), 7.59 (d, J=7.0 Hz, 2H), 7.48-7.39 (m, 2H), 7.36 (t, J=7.0 Hz, 1H), 7.24 (d, J=4.3 Hz, 2H), 4.50-4.44 (m, 2H), 2.37 (s, 3H).

Workup

  1. stirringthe reaction mixture stirred at 105° C. for 18 h
  2. customthen purified by preparative HPLC (RT=8.79 min using Axia Luna 5 u C18 30×100 mm column with flow rate of 40 mL/min over 10 min period. Solvent A=10/90/0.1% ACN/H2O/TFA, Solvent B=90/10/0.1%, 10 to 100% B)
  3. additionThe fraction containing product
  4. customwas evaporated to dryness
  5. customthe residue chromatographed on silica gel eluting with 0 to 10% MeOH/DCM

Sources & evidence

ORD record
ord-1567b97ad08e432ca33e7a68c439319d
Source dataset
uspto-grants-2015_10
Patent number
US09169240B2

Reaction notes

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