2,2,6,6-Tetramethylpiperidine → HCID 178501174, compound

HRID 518609Notes

Reaction equation

HRID 518609 reaction equation
[C:1]([NH:9][C:10]1[N:14]([C@@H:15]2[CH2:20][CH2:19][C@H:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:17][CH2:16]2)[C:13]2[CH:25]=[C:26]([CH2:29]O)[CH:27]=[CH:28][C:12]=2[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:35][C:36]1([CH3:44])[CH2:41][CH2:40][CH2:39][C:38]([CH3:43])([CH3:42])[NH:37]1>C(Cl)Cl>[C:1]([NH:9][C:10]1[N:14]([C@@H:15]2[CH2:16][CH2:17][C@H:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:19][CH2:20]2)[C:13]2[CH:25]=[C:26]([CH2:29][N:37]3[C:38]([CH3:43])([CH3:42])[CH2:39][CH2:40][CH2:41][C:36]3([CH3:44])[CH3:35])[CH:27]=[CH:28][C:12]=2[N:11]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 130352,2,6,6-TetramethylpiperidineHCID 24386Thionyl ChlorideHCID 178501175HCID 178501175, compound

Product 1

HCID 178501174HCID 178501174, compoundYield 30.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

cis-Methyl 4-(2-benzamido-6-(hydroxymethyl)-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate (0.05 g, 0.123 mmol) was suspended in DCM (1.2 mL) and cooled to 0° C. under nitrogen atmosphere. To this mixture was added thionyl chloride (0.292 g, 2.454 mmol), and the mixture was stirred for 30 minutes. The resulting mixture was concentrated under reduced pressure and dried under high vacuum. The residue was suspended in 2 mL of DMSO and cooled in an ice bath under nitrogen atmosphere. To this mixture was added 2,2,6,6-tetramethylpiperidine (0.173 g, 1.227 mmol) dropwise, and the reaction was stirred in an ice bath for 30 minutes and at RT for another 30 minutes. The reaction mixture was diluted with DCM (20 mL) and washed with water (10 mL). The organic layer was collected, dried over sodium sulfate, and concentrated under vacuum. The residual yellow oil was triturated with 10% water/MeOH to afford cis-methyl 4-(2-benzamido-6-((2,2,6,6-tetramethylpiperidin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate (20 mg, 30.8% yield). MS m/z=531.2 [M+H]. Calc'd for C32H42N4O3: 530.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04 (s, 12H) 1.54-1.73 (m, 6H) 1.73-1.99 (m, 4H) 2.25-2.41 (m, 2H) 2.46-2.54 (m, 2H) 2.84-3.02 (m, 1H) 3.81 (s, 3H) 3.93 (s, 2H) 4.73-5.08 (m, 1H) 7.25 (d, J=8.31 Hz, 1H) 7.39-7.62 (m, 4H) 7.74 (s, 1H) 8.23-8.35 (m, 2H) 12.76 (s, 1H).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. customdried under high vacuum
  3. temperaturecooled in an ice bath under nitrogen atmosphere
  4. stirringthe reaction was stirred in an ice bath for 30 minutes and at RT for another 30 minutes
  5. washwashed with water (10 mL)
  6. customThe organic layer was collected
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe residual yellow oil was triturated with 10% water/MeOH

Sources & evidence

ORD record
ord-1da15d02b91744978b5295de39d64abb
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

Loading…