Pyridine → Tetrahydro-pyran-4-carboxylic acid {4-[(S)-3-((S)-2-methyl-pyrrolidin-1-yl)-cyclopentyl]-phenyl}-amide

HRID 1027437Notes

Reaction equation

HRID 1027437 reaction equation
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH:7]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)[CH2:8]1.[O:19]1[CH2:24][CH2:23][CH:22]([C:25](Cl)=[O:26])[CH2:21][CH2:20]1.N1C=CC=CC=1.N.CO>C(Cl)Cl>[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH:7]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:25]([CH:22]3[CH2:23][CH2:24][O:19][CH2:20][CH2:21]3)=[O:26])=[CH:14][CH:13]=2)[CH2:8]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 2795505Oxane-4-carbonyl chlorideHCID 21705897Ammonia methanolHCID 674791474-[(S)-3-((S)-2-Methyl-pyrrolidin-1-yl)-cyclopentyl]-phenylamine2×

Product 1

HCID 68212297Tetrahydro-pyran-4-carboxylic acid {4-[(S)-3-((S)-2-methyl-pyrrolidin-1-yl)-cyclopentyl]-phenyl}-amideYield 87.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

4-[(S)-3-((S)-2-Methyl-pyrrolidin-1-yl)-cyclopentyl]-phenylamine (Intermediate 14) (40 mg, 0.16 mmol) was dissolved in DCM (2 mL). To this solution was transferred a solution of tetrahydro-pyran-4-carboxylic acid chloride (71.3 mg, 0.5 mmol, 3.0 equiv.) in DCM (1 mL), followed by pyridine (0.5 mL). The solution was stirred at r.t. for 2 h when TLC (5% of 7N NH3 MeOH in DCM) and LC/MS showed that the reaction was complete. The reaction was quenched by addition of polymer bound diethylenetriamine (4 mmol/g) (0.1 g) and the suspension was stirred for 30 min. Then, 10 mL of DCM was added to the suspension and the suspension was filtered through a celite pad, rinsed with DCM and 10% MeOH in DCM. The crude product was purified on a silica gel column eluted with 5% of 7N NH3 MeOH in DCM to obtain 50 mg (87% yield) of the title compound.

Workup

  1. customThe reaction was quenched by addition of polymer
  2. additionThen, 10 mL of DCM was added to the suspension
  3. filtrationthe suspension was filtered through a celite pad
  4. washrinsed with DCM and 10% MeOH in DCM
  5. customThe crude product was purified on a silica gel column
  6. washeluted with 5% of 7N NH3 MeOH in DCM

Sources & evidence

ORD record
ord-ee9250e0a1f2407b8e697ec71a512448
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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