Tetrahydrofuran → 5-(1-benzylpyrrolidin-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

HRID 1473424Notes

Reaction equation

HRID 1473424 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][C:17]([S:23](OC1C(F)=C(F)C(F)=C(F)C=1F)(=[O:25])=[O:24])=[CH:18]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:38]1[C:42]([NH2:43])=[N:41][CH:40]=[N:39]1.C1COCC1.CC([O-])(C)C.[Li+]>C(Cl)Cl>[CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][C:17]([S:23]([NH:43][C:42]1[S:38][N:39]=[CH:40][N:41]=1)(=[O:25])=[O:24])=[CH:18]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2902745-Amino-1,2,4-thiadiazoleHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 86687401Perfluorophenyl 5-(1-benzylpyrrolidin-2-yl)naphthalene-2-sulfonate

Product 1

HCID 715866045-(1-benzylpyrrolidin-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamideYield 60.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A flask was charged with perfluorophenyl 5-(1-benzylpyrrolidin-2-yl)naphthalene-2-sulfonate (INTERMEDIATE LL) (24.8 mg, 0.046 mmol), 1,2,4-thiadiazol-5-amine (5.64 mg, 0.056 mmol), and THF (465 μl) to give a clear, colorless solution. The flask was cooled in an ice-bath for 5 min, then lithium 2-methylpropan-2-olate (1M in hexane) (102 μl, 0.102 mmol) was added dropwise. After 1 h, the mixture was loaded directly onto a 5-g silica gel loading column with the aid of DCM. The column was dried under vacuum, then eluted onto a prequilibrated 12-g silica gel column with 0 to 10% MeOH/DCM to give 5-(1-benzylpyrrolidin-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (12.69 mg, 0.028 mmol, 60.6% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=8.46-8.33 (m, 2H), 8.07 (d, J=8.0 Hz, 1H), 8.02 (s, 1H), 7.97 (d, J=7.1 Hz, 1H), 7.83 (dd, J=1.9, 8.9 Hz, 1H), 7.65 (t, J=7.7 Hz, 1H), 7.34-7.21 (m, 5H), 4.62 (br. s., 1H), 3.91 (d, J=13.0 Hz, 1H), 3.24 (br. s., 4H), 1.97 (d, J=14.1 Hz, 2H), 1.86-1.72 (m, 1H); m/z (ESI) 451.4 (M+H)+.

Workup

  1. customto give a clear, colorless solution
  2. temperatureThe flask was cooled in an ice-bath for 5 min
  3. customThe column was dried under vacuum
  4. washeluted onto a prequilibrated 12-g silica gel column with 0 to 10% MeOH/DCM

Sources & evidence

ORD record
ord-ca0f4fa2f6244aefa9a4a232a198b47c
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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