Dimethylamine → (2S,4S)-tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2-(dimethylcarbamoyl)piperidine-1-carboxylate

HRID 876423Notes

Reaction equation

HRID 876423 reaction equation
[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@H:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:23]([C:34](O)=[O:35])[CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.C[CH2:38][N:39]=[C:40]=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.CNC>C(Cl)Cl.CCOC(C)=O>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@H:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])[C@H:23]([C:34](=[O:35])[N:39]([CH3:40])[CH3:38])[CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

8

Reactant 5

HCID 674DimethylamineHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 67230757(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid

Product 1

HCID 67234046(2S,4S)-tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2-(dimethylcarbamoyl)piperidine-1-carboxylateYield 75.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (Example 53; 0.100 g, 0.204 mmol), EDCI (0.0548 g, 0.286 mmol) and HOBT (0.0373 g, 0.276 mmol) were mixed in CH2Cl2 (2.5 mL) and the mixture was cooled to 0° C. Triethylamine (0.0712 mL, 0.511 mmol) was added and the mixture stirred for 15 minutes. Dimethylamine (0.153 mL, 0.306 mmol, 2.0M in THF) was added, and the mixture was warmed to ambient temperature and stirred for 5.0 hours. The mixture was diluted with EtOAc (20 mL) and washed with 1N KHSO4 (2×10 mL), followed by saturated aqueous NaHCO3, and brine. The organics were dried over MgSO4, filtered and concentrated, then purified by column chromatography (1 to 5% MeOH/CH2Cl2) to afford 0.080 g (75%) of the desired product.

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for 5.0 hours
  3. washwashed with 1N KHSO4 (2×10 mL)
  4. dry with materialThe organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography (1 to 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-82ce31f6e46d4e38aab21f45f00129a7
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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