Benzyl Isothiocyanate → 6-[(benzylcarbamothioyl)amino]-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-5-ium trifluoroacetate

HRID 571401Notes

Reaction equation

HRID 571401 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[C:12]3[CH:13]=[N:14][C:15]([NH2:17])=[CH:16][C:11]=3[N:10](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[N:37]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[C:38]=[S:39].[C:47]([OH:53])([C:49]([F:52])([F:51])[F:50])=[O:48].C([SiH](CC)CC)C>C1(C)C=CC=CC=1>[F:50][C:49]([F:52])([F:51])[C:47]([O-:53])=[O:48].[CH2:40]([NH:37][C:38]([NH:17][C:15]1[NH+:14]=[CH:13][C:12]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=3)=[N:9][NH:10][C:11]=2[CH:16]=1)=[S:39])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 2346Benzyl IsothiocyanateHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 895258183-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine2×

Product 1

HCID 1176016386-[(benzylcarbamothioyl)amino]-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-5-ium trifluoroacetateYield 27%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 3-(2-methylpyridin-4-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (intermediate 5a; 25 mg, 0.05 mmol) in toluene (1 mL) was treated with (isothiocyanatomethyl)benzene (15 mg, 0.1 mmol) and the mixture was heated at 100° C. overnight. The volatiles were concentrated in vacuo and the residue was directly dissolved in DCM (0.8 mL), treated with TFA (0.2 mL) and triethylsilane (0.008 mL, 0.051 mmol) and left under stirring for 5 h, then concentrated in vacuo and purified by MS-directed reverse phase preparative-HPLC (C-18 stationary phase, eluting with a H2O/MeCN gradient with 0.1% TFA) to yield 6-[(benzylcarbamothioyl)amino]-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-5-ium trifluoroacetate as a yellow solid (7 mg, 0.014 mmol, 27%). MS ESI calc'd. for C20H19N6S [M+1]+ 375, found 375.

Workup

  1. concentrationThe volatiles were concentrated in vacuo
  2. dissolutionthe residue was directly dissolved in DCM (0.8 mL)
  3. waitleft
  4. concentrationconcentrated in vacuo
  5. custompurified by MS-directed reverse phase preparative-HPLC (C-18 stationary phase
  6. washeluting with a H2O/MeCN gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-77265b85697b4309aa0698e1e7d5f137
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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