Sodium methanethiolate → 6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-N-((1R,2R)-2-(methylthio)cyclohexyl)benzo[d]thiazol-2-amine

HRID 1848219Notes

Reaction equation

HRID 1848219 reaction equation
CS(O[C@H:6]1[CH2:11][CH2:10][CH2:9][CH2:8][C@H:7]1[NH:12][C:13]1[S:14][C:15]2[CH:21]=[C:20]([CH2:22][N:23]3[C:27]4=[N:28][CH:29]=[C:30]([F:32])[CH:31]=[C:26]4[N:25]=[CH:24]3)[CH:19]=[CH:18][C:16]=2[N:17]=1)(=O)=O.[CH3:33][S-:34].[Na+]>CN(C=O)C>[F:32][C:30]1[CH:31]=[C:26]2[N:25]=[CH:24][N:23]([CH2:22][C:20]3[CH:19]=[CH:18][C:16]4[N:17]=[C:13]([NH:12][C@@H:7]5[CH2:8][CH2:9][CH2:10][CH2:11][C@H:6]5[S:34][CH3:33])[S:14][C:15]=4[CH:21]=3)[C:27]2=[N:28][CH:29]=1

Participants

4

Reactant 2

HCID 4378561Sodium methanethiolateHCID 86681195(1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexyl methanesulfonate

Product 1

HCID 866811966-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-N-((1R,2R)-2-(methylthio)cyclohexyl)benzo[d]thiazol-2-amineYield 5.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (1S,2R)-2-((6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexyl methanesulfonate (100 mg, 0.2 mmol) and sodium thiomethoxide (74 mg, 1.0 mmol) in DMF (1.0 mL) was stirred at rt for 2 h. The mixture was purified directly by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford 6-((6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)-N-((1R,2R)-2-(methylthio)cyclohexyl)benzo[d]thiazol-2-amine (5 mg, 4%) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.41 (t, J=1.8 Hz, 1H), 8.04-8.11 (m, 2H), 7.67 (s, 1H), 7.30 (m, 1H), 7.23 (m, 1H), 5.48 (s, 2H), 3.72 (m, 1H), 2.56 (m, 1H), 1.99-2.08 (m, 5H), 1.63-1.71 (m, 2H), 1.41-1.51 (m, 1H), 1.21-1.36 (m, 3H); LCMS (ESI) m/z 428 (M+H)+.

Workup

  1. customThe mixture was purified directly by reverse-phase preparative HPLC
  2. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-06de2842c4204fc6bab738bf358e3ed0
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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