N,N-Dimethylethylenediamine → HCID 86681076, compound

HRID 1848102Notes

Reaction equation

HRID 1848102 reaction equation
Br[C:2]1[CH:28]=[CH:27][C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[CH3:29][S:30]([O-:32])=[O:31].[Na+].CN(C)CCN>>[CH3:29][S:30]([C:2]1[CH:28]=[CH:27][C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1)(=[O:32])=[O:31]

Participants

4

Reactant 3

HCID 66053N,N-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 71549044HCID 71549044, compound

Product 1

HCID 86681076HCID 86681076, compoundYield 30%

Conditions

Temperature
125 °C

Procedure

A stirred suspension of (1R,2R)-2-((6-((5-bromo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (100 mg, 0.22 mmol) (prepared as described in Example 108, steps 1 through 6), sodium methane sulfinate (89 mg, 0.9 mmol) and N,N-dimethylethylenediamine (9.6 μL, 0.9 mmol) was degassed under a stream of argon for 5 min. Copper (I) trifluoromethane-sulfonate benzene complex (22 mg, 0.04 mmol) was added and the mixture was sealed and heated at 125° C. for 7 h. The mixture was cooled to rt, filtered, and the filtrate subjected to purification by reverse-phase preparative HPLC eluting with a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and a Varian diphenyl column as the stationary phase, to afford (1R,2R)-2-((6-((5-(methylsulfonyl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (30 mg, 30%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 8.69 (s, 1H), 8.20 (s, 1H), 8.06 (d, J=7.5 Hz, 1H), 7.84 (m, 1H), 7.76 (m, 1H), 7.69 (s, 1H), 7.30 (m, 1H), 7.21 (m, 1H), 5.56 (s, 2H), 4.82 (m, 1H), 3.50 (m, 1H), 3.36 (m, 1H), 3.19 (s, 3H), 2.01 (m, 1H), 1.87 (m, 1H), 1.56-1.67 (m, 2H), 1.11-1.31 (m, 4H); LCMS (ESI) m/z 457 (M+H)+.

Workup

  1. customwas degassed under a stream of argon for 5 min
  2. additionCopper (I) trifluoromethane-sulfonate benzene complex (22 mg, 0.04 mmol) was added
  3. customthe mixture was sealed
  4. temperatureThe mixture was cooled to rt
  5. filtrationfiltered
  6. customthe filtrate subjected to purification by reverse-phase preparative HPLC
  7. washeluting with a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase

Sources & evidence

ORD record
ord-db07c990f10743b08f6f39a21f7a82fb
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…