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Pyridine → (R)-tert-butyl 1-(5-bromo-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate hydrochloride

HRID 2203938
Notes
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Reaction equation

HRID 2203938 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([Br:26])[C:9]=2[N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:12]2)[NH:4][CH:3]=1.N1C=CC=CC=1.[CH:33]1([C:36]([Cl:38])=[O:37])[CH2:35][CH2:34]1.O[Li].O>CN1C(=O)CCC1.CCOC(C)=O.CC#N.O>[ClH:38].[Br:26][C:8]1[C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])[CH2:12]2)=[C:10]2[C:2]([NH:1][C:36]([CH:33]3[CH2:35][CH2:34]3)=[O:37])=[CH:3][NH:4][C:5]2=[N:6][CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 1049PyridineHCID 77637Cyclopropanecarbonyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 67045616(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate

Product 1

HCID 67045096(R)-tert-butyl 1-(5-bromo-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate hydrochloride
Yield 36%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

A solution of (R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate (305 mg, 0.7188 mmol) in NMP (3 mL) was cooled to 0° C. and pyridine (1.5 mL) was added. Then the mixture was treated dropwise with cyclopropanecarbonyl chloride (195.7 μL, 2.156 mmol) and stirred at 0° C. for 30 minutes. 2M LiOH.H2O (4 mL) was then added, and the mixture was stirred at room temperature. After 48 hours, the mixture was diluted with EtOAc (100 mL) and washed with water (3×20 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, 35 CV) to provide (R)-tert-butyl 1-(5-bromo-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl(methyl)carbamate hydrochloride (127 mg, 36% yield) as a solid. LCMS (APCI+) m/z 492 (M+H)+.

Workup

  1. stirringthe mixture was stirred at room temperature
  2. waitAfter 48 hours
  3. washwashed with water (3×20 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-0b02e78cc87d41b48e929c108cfe7819
Source dataset
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09365568B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes