Sodium Hydroxide → HCID 71550417, compound

HRID 1848046Notes

Reaction equation

HRID 1848046 reaction equation
Br[C:2]1[C:28]([O:29][CH3:30])=[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.[OH-].[Na+]>O1CCOCC1.[Zn]>[CH3:30][O:29][C:28]1[CH:2]=[CH:3][C:4]2[N:8]=[CH:7][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)[C:5]=2[CH:27]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71550134HCID 71550134, compound

Product 1

HCID 71550417HCID 71550417, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of (1R,2R)-2-((6-((5-bromo-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (100 mg, 0.2 mmol) from Step 1 of Example 51 in 1,4-dioxane (1.4 mL) and aq 1 N NaOH (300 mL) was added zinc powder (134 mg, 2 mmol). The mixture was heated at 80° C. for 55 h. The mixture was cooled to rt, filtered, and the filtrate was purified 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 (1R,2R)-2-((6-((6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (45 mg, 56%) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ 8.23 (s, 1H), 7.98 (d, J=7.6 Hz, 1H), 7.64 (d, J=1.0 Hz, 1H), 7.51 (d, J=8.6 Hz, 1H), 7.29 (d, J=8.4 Hz, 1H), 7.20 (dd, J=1.4, 8.2 Hz, 1H), 7.12 (d, J=2.2 Hz, 1H), 6.80 (dd, J=2.3, 8.7 Hz, 1H), 5.41 (s, 2H), 4.76 (m, 1H), 3.76 (s, 3H), 3.51 (m, 1H), 3.33 (m, 1H), 2.03 (m, 1H), 1.87 (m, 1H), 1.56-1.66 (m, 2H), 1.14-1.29 (m, 4H). LCMS (ESI) m/z 410 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. filtrationfiltered
  3. customthe filtrate was purified by reverse-phase preparative HPLC
  4. 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-e00fe5ca4c7043b0b6412cddb1f1248f
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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