2-Piperidone → HCID 86681216, compound

HRID 1848243Notes

Reaction equation

HRID 1848243 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].I[C:10]1[CH:36]=[CH:35][C:13]2[N:14]([CH2:17][C:18]3[CH:34]=[CH:33][C:21]4[N:22]=[C:23]([NH:25][C@@H:26]5[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]5[OH:32])[S:24][C:20]=4[CH:19]=3)[CH:15]=[N:16][C:12]=2[CH:11]=1.[NH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][C:38]1=[O:43]>CS(C)=O.[Cu](I)I>[OH:32][C@@H:27]1[CH2:28][CH2:29][CH2:30][CH2:31][C@H:26]1[NH:25][C:23]1[S:24][C:20]2[CH:19]=[C:18]([CH2:17][N:14]3[C:13]4[CH:35]=[CH:36][C:10]([N:37]5[CH2:42][CH2:41][CH2:40][CH2:39][C:38]5=[O:43])=[CH:11][C:12]=4[N:16]=[CH:15]3)[CH:34]=[CH:33][C:21]=2[N:22]=1

Participants

6

Reactant 3

HCID 126652-PiperidoneHCID 62657Potassium Phosphate, TribasicHCID 86681193HCID 86681193, compound

Product 1

HCID 86681216HCID 86681216, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
125 °C

Procedure

To a stirred mixture of copper iodide (23 mg, 0.12 mmol) and tripotassium phosphate (190 mg, 0.90 mmol) in DMSO (3 mL) were added (1R,2R)-2-((6-((5-iodo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (150 mg, 0.30 mmol) from Step 5 of Example 183 and piperidin-2-one (200 mg, 2.02 mmol). The mixture was flushed with argon and heated in a sealed reaction vessel at 125° C. for 15 h. The reaction mixture was cooled to rt and filtered, and the filtrate was purified directly by reverse-phase preparative 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 1-(1-((2-(((1R,2R)-2-Hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)piperidin-2-one (3 mg, 7%) as a solid. 1H NMR (500 MHz, DMSO-d6) δ 8.31 (br s, 1H), 7.69 (br s, 1H), 7.62 (s, 1H), 7.44-7.53 (m, 2H), 7.30 (d, J=8.4 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 7.08 (d, J=8.9 Hz, 1H), 5.45 (s, 2H), 3.62 (t, J=5.4 Hz, 2H), 3.51 (br s, 1H), 3.37-3.46 (m, 2H), 2.36-2.43 (m, 2H), 2.06 (m, 1H), 1.82-1.93 (m, 5H), 1.61-1.70 (m, 2H), 1.20-1.36 (m, 4H); LCMS (ESI) m/z 476 (M+H)+.

Workup

  1. customThe mixture was flushed with argon
  2. temperatureThe reaction mixture was cooled to rt
  3. filtrationfiltered
  4. customthe filtrate was purified directly by reverse-phase preparative HPLC
  5. 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-b765182cd41d4e3f8680bb9218515116
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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