Ethyl 4-piperidinecarboxylate → 1-{4-[2-Cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]-benzenesulfonyl}-piperidine-4-carboxylic acid ethyl ester

HRID 1712994Notes

Reaction equation

HRID 1712994 reaction equation
[CH:1]1([CH2:6][CH:7]([C:22]2[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=2)[C:8](=[O:21])[NH:9][C:10]2[S:11][C:12]3[C:17]([N:18]=2)=[CH:16][CH:15]=[C:14]([O:19][CH3:20])[N:13]=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:32]([O:34][C:35]([CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)=[O:36])[CH3:33].C(N(C(C)C)CC)(C)C>ClCCl>[CH2:32]([O:34][C:35]([CH:37]1[CH2:42][CH2:41][N:40]([S:28]([C:25]2[CH:24]=[CH:23][C:22]([CH:7]([C:8](=[O:21])[NH:9][C:10]3[S:11][C:12]4[C:17]([N:18]=3)=[CH:16][CH:15]=[C:14]([O:19][CH3:20])[N:13]=4)[CH2:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:27][CH:26]=2)(=[O:30])=[O:29])[CH2:39][CH2:38]1)=[O:36])[CH3:33]

Participants

5

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 81531DiisopropylethylamineHCID 444741674-[2-Cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]-benzenesulfonyl chloride

Product 1

HCID 866257401-{4-[2-Cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]-benzenesulfonyl}-piperidine-4-carboxylic acid ethyl esterYield 71.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Title compound E, 4-[2-Cyclopentyl-1-(5-methoxy-thiazolo[5,4-b]pyridin-2-ylcarbamoyl)-ethyl]-benzenesulfonyl chloride (120 mg, 0.2499 mmol) was dissolved in dichloromethane. To this was added a solution of piperidine-4-carboxylic acid ethyl ester (38 μL, 0.2499 mmol) and diisopropylethylamine (87 μL, 0.4998 mmol) in dichloromethane. The reaction was stirred at room temperature for 1 hour, then concentrated. The residue was partitioned between 1N hydrochloric acid and ethyl acetate. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford a yellow oil. The crude was then purified via column chromatography 10-90% ethyl acetate in hexanes to afford the desired product as a yellow foam (107 mg, 71%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.20 (t, J=7.07 Hz, 3 H) 1.10-1.22 (m, 2 H) 1.50 (d, J=2.78 Hz, 2 H) 1.49 (br. s., 1 H) 1.63 (dd, J=14.91, 7.83 Hz, 2 H) 1.62 (br. s., 1 H) 1.81 (dd, J=13.64, 3.79 Hz, 3 H) 1.95 (t, J=7.07 Hz, 2 H) 1.91 (d, J=7.83 Hz, 1 H) 2.21-2.31 (m, 2 H) 2.53 (td, J=11.43, 2.91 Hz, 2 H) 3.61-3.71 (m, 3 H) 4.00 (s, 3 H) 4.09 (q, J=7.07 Hz, 2 H) 6.80 (d, J=8.84 Hz, 1 H) 7.52 (d, J=8.59 Hz, 2 H) 7.74-7.84 (m, 3 H) LC/MS 601.3 (M+1) 599.4 (M−1)

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between 1N hydrochloric acid and ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a yellow oil
  8. customThe crude was then purified via column chromatography 10-90% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6390c9f55c93493aacbb49cf4b8223ea
Source dataset
uspto-grants-2010_09
Patent number
US07795257B2

Reaction notes

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