Lithium Hydroxide → methyl N-[(1R,3S)-3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]carbamate

HRID 526950Notes

Reaction equation

HRID 526950 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15](S(C)=O)[C:14]([F:20])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[NH2:31][C@H:32]1[CH2:37][CH2:36][CH2:35][C@@H:34]([NH:38][C:39](=[O:42])[O:40][CH3:41])[CH2:33]1.[OH-].[Li+]>C1COCC1.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:31][C@H:32]4[CH2:37][CH2:36][CH2:35][C@@H:34]([NH:38][C:39](=[O:42])[O:40][CH3:41])[CH2:33]4)[C:14]([F:20])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 3939Lithium HydroxideHCID 672853215-Chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridineHCID 68007555methyl N-[(1R,3S)-3-aminocyclohexyl]carbamate2×

Product 1

HCID 68008354methyl N-[(1R,3S)-3-[[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

5-chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)-pyrrolo[2,3-b]pyridine, 19b, (2.04 g, 4.39 mmol) and methyl N-[(1R,3S)-3-aminocyclohexyl]carbamate (0.60 g, 3.14 mmol) were suspended in THF (16 mL) and heated in the microwave to 130° C. for 20 minutes. Lithium hydroxide (15.67 mL of 1M solution, 15.67 mmol) was added, and the resulting mixture was heated in the microwave for 20 min at 130° C. The resulting solution was diluted with water (150 mL) and ethyl acetate (200 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (100 mL) and t organic layers were combined, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography (40-100% EtOAc/hexanes) followed by treatment of the pure fractions with 4N HCl in dioxane to provide the hydrochloride of compound, 570, as an off white solid.

Workup

  1. temperaturethe resulting mixture was heated in the microwave for 20 min at 130° C
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (100 mL) and t organic layers
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography (40-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5b8cc260f46e43c59bb32af9a9b59212
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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