Diisopropylethylamine → tert-butyl (R)-1-(3-((R)-2-methoxypropanamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 2203974Notes

Reaction equation

HRID 2203974 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.C(N(CC)C(C)C)(C)C.Cl[C:25]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][N:28]=[C:27]2[NH:35][CH:36]=[C:37]([NH:38][C:39](=[O:44])[C@H:40]([O:42][CH3:43])[CH3:41])[C:26]=12>CCCCO.O>[CH3:43][O:42][C@H:40]([CH3:41])[C:39]([NH:38][C:37]1[C:26]2[C:27](=[N:28][CH:29]=[C:30]([C:31]([F:34])([F:32])[F:33])[C:25]=2[N:1]2[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)[NH:35][CH:36]=1)=[O:44]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 60205658HCID 60205658, compound

Product 1

HCID 60205659tert-butyl (R)-1-(3-((R)-2-methoxypropanamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 41%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

(R)-tert-Butyl piperidin-3-ylcarbamate (456 mg, 2.28 mmol) and N,N-diisopropylethylamine (294 mg, 0.396 mL, 2.28 mmol) were added to a suspension of (R)—N-(4-chloro-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide (244 mg, 0.759 mmol) in n-BuOH (3 mL). The resulting mixture was heated in a sealed tube under a nitrogen atmosphere at 160° C. for 24 hours. The cooled mixture was diluted with water and extracted with EtOAc (3×20 mL). The combined organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated to an oil, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 15-80% CH3CN/water, 25CV) to give tert-butyl (R)-1-(3-((R)-2-methoxypropanamido)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (151 mg, 41%) as a solid. LCMS (APCI+) m/z 386.1, 486.1 (M+H)+, Retention time=3.85 minutes.

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated to an oil, which
  5. customwas purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-28d485d877fd43aaa659b0e2ef521a51
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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