Triethylamine → (R)-tert-butyl 1-(5-chloro-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 408350Notes

Reaction equation

HRID 408350 reaction equation
C(N(CC)CC)C.[NH2:8][C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([Cl:32])[C:16]=2[N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:19]2)[NH:11][CH:10]=1.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1.O[Li].O>CN1C(=O)CCC1.C(Cl)Cl.CO.CCOC(C)=O>[Cl:32][C:15]1[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[CH2:19]2)=[C:17]2[C:9]([NH:8][C:36]([CH:33]3[CH2:35][CH2:34]3)=[O:37])=[CH:10][NH:11][C:12]2=[N:13][CH:14]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 67045610(R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045317(R)-tert-butyl 1-(5-chloro-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (1018 μL, 7.462 mmol) was added to an aliquot of (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (390 mg, 1.066 mmol; Example 91, Step A) in NMP (3 mL) at 0° C. under N2 atmosphere. The mixture was treated dropwise with cyclopropanecarbonyl chloride (580.4 μL, 6.396 mmol) and stirred at 0° C. for 1 hour. The reaction mixture was then diluted with CH2Cl2 (4 mL). 2M LiOH.H2O (9 mL) was added, and the mixture was allowed to stir for 24 hours. The mixture was then diluted with 2% MeOH/EtOAc (100 mL) and washed with water (4×20 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by reverse phase chromatography (Biotage SP4, C-18 40M+, 15-85% CH3CN/water, 38 CV) to provide (R)-tert-butyl 1-(5-chloro-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate as a solid.

Workup

  1. stirringto stir for 24 hours
  2. washwashed with water (4×20 mL)
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue obtained
  8. customwas purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-9f51e65745c6410484108a4d2138a077
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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