N,N-Dimethylethylenediamine → (1R,2R)-2-((6-((5-(methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

HRID 1848092Notes

Reaction equation

HRID 1848092 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]5[OH:26])[S:18][C:14]=4[CH:13]=3)[CH:9]=[N:10][C:5]2=[CH:4][CH:3]=1.[CH3:29][S:30]([O-:32])=[O:31].[Na+].CN(C)CCN>CS(C)=O>[CH3:29][S:30]([C:2]1[N:7]=[C:6]2[N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]5[OH:26])[S:18][C:14]=4[CH:13]=3)[CH:9]=[N:10][C:5]2=[CH:4][CH:3]=1)(=[O:32])=[O:31]

Participants

5

Reactant 3

HCID 66053N,N-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 71550847(1R,2R)-2-((6-((5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Product 1

HCID 71549048(1R,2R)-2-((6-((5-(methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanolYield 37.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
125 °C

Procedure

A stirred mixture of (1R,2R)-2-((6-((5-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (89 mg, 0.194 mmol) from Example 78, sodium methane sulfinate (80 mg, 0.777 mmol), and N,N-dimethylethylenediamine (7 mg, 0.078 mmol) in anhydrous DMSO (2 mL) at rt was purged for 15 min with a stream of argon. To the resulting mixture was added copper (I) trifluoromethane-sulfonate benzene complex (20 mg, 0.038 mmol). The reaction vessel was sealed and the mixture was stirred at 125° C. for 5 h. After cooling to rt, the reaction mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((5-(methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (33 mg, 37%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.91 (s, 1H), 8.39 (d, J=8.3 Hz, 1H), 7.90-8.02 (m, 2H), 7.78 (s, 1H), 7.25-7.36 (m, 2H), 5.54 (s, 2H), 4.74 (br s, 1H), 3.50 (br s, 1H), 3.33-3.34 (m, 4H), 2.02 (m, 1H), 1.87 (m, 1H), 1.55-1.65 (m, 2H), 1.15-1.30 (m, 4H); LCMS (ESI) m/z 458 (M+H)+.

Workup

  1. customwas purged for 15 min with a stream of argon
  2. additionTo the resulting mixture was added copper (I) trifluoromethane-sulfonate benzene complex (20 mg, 0.038 mmol)
  3. customThe reaction vessel was sealed
  4. temperatureAfter cooling to rt
  5. customthe reaction mixture was purified directly by reverse-phase
  6. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-b772774c07fe427288552fb44573ff31
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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