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

HRID 875835Notes

Reaction equation

HRID 875835 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.[CH3:33][CH:34]([CH3:39])[CH2:35][C:36](Cl)=[O:37].CC#N.O>CN1C(=O)CCC1.C(Cl)Cl.O[Li].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](=[O:37])[CH2:35][CH:34]([CH3:39])[CH3:33])=[CH:10][NH:11][C:12]2=[N:13][CH:14]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 66054Isovaleryl chlorideHCID 18373917Acetonitrile--water (1/1)HCID 67045610(R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045858(R)-tert-butyl 1-(5-chloro-3-(3-methylbutanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateYield 53%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolventHCID 168937Lithium hydroxide, monohydrateSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (522 μL, 3.83 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 (200 mg, 0.547 mmol) in NMP (3 mL) at 0° C. under N2 atmosphere. The mixture was then treated dropwise with 3-methylbutanoyl chloride (231 mg, 1.91 mmol) and stirred at 0° C. After 1 hour, the reaction mixture was diluted with CH2Cl2 (4 mL), and 2M LiOH.H2O (3 mL) was added. The resulting mixture was stirred at room temperature for 18 hours. The mixture was then diluted with additional CH2Cl2 (50 mL) and washed with water (3×10 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by reverse phase chromatography (Biotage SP4, C-18 40M+, 15-85% CH3CN/water, 40 CV) to provide (R)-tert-butyl 1-(5-chloro-3-(3-methylbutanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (130 mg, 53% yield) as a solid.

Workup

  1. additionwas added
  2. stirringThe resulting mixture was stirred at room temperature for 18 hours
  3. washwashed with water (3×10 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-b85975068929452585d80af3fe6db7bf
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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