2-Aminothiazole → 5-(1-benzylpyrrolidin-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide

HRID 1473425Notes

Reaction equation

HRID 1473425 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[CH:42]=[CH:41][N:40]=[C:39]1[NH2:43].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:39]1[S:38][CH:42]=[CH:41][N:40]=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 21552-AminothiazoleHCID 8028TetrahydrofuranHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 86687401Perfluorophenyl 5-(1-benzylpyrrolidin-2-yl)naphthalene-2-sulfonate

Product 1

HCID 715866055-(1-benzylpyrrolidin-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamideYield 87.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A flask was charged with perfluorophenyl 5-(1-benzylpyrrolidin-2-yl)naphthalene-2-sulfonate (Intermediate LL, 21.5 mg, 0.040 mmol), thiazol-2-amine (4.84 mg, 0.048 mmol), and THF (403 μl) to give a clear, colorless solution. The flask was cooled in an dry ice-acetone bath for 5 min, then lithium 2-methylpropan-2-olate (1M in hexane) (89 μl, 0.089 mmol) was added dropwise. The resulting mixture was stirred for 1 min, then the flask was lowered into an ice-bath. After 1 h, the mixture was warmed to room temperature then 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 column with 0 to 10% MeOH/DCM to give 5-(1-benzylpyrrolidin-2-yl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide (15.85 mg, 0.035 mmol, 87% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.97-12.23 (m, 1H), 8.51 (d, J=9.1 Hz, 1H), 8.46 (d, J=1.9 Hz, 1H), 8.09-7.96 (m, 2H), 7.83 (dd, J=2.1, 9.0 Hz, 1H), 7.69-7.61 (m, 1H), 7.29 (d, J=4.4 Hz, 4H), 7.27-7.24 (m, 1H), 7.24-7.20 (m, 1H), 6.83 (d, J=4.6 Hz, 1H), 4.16 (t, J=8.2 Hz, 1H), 3.78 (d, J=13.2 Hz, 1H), 3.15 (d, J=13.2 Hz, 1H), 3.07 (td, J=4.6, 9.1 Hz, 1H), 2.47-2.38 (m, 1H), 2.30 (q, J=8.6 Hz, 1H), 1.89-1.79 (m, 2H), 1.68-1.57 (m, 1H); m/z (ESI) 450.4 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-5e6ae685eb02419f9566e00c234a3970
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…