Sodium Carbonate → 2-((1S,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-1-hydroxycyclohexyl)ethanenitrile

HRID 75037

Reaction equation

HRID 75037 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.Cl[C:31]1[N:36]=[C:35]([NH:37][C@H:38]2[CH2:43][CH2:42][CH2:41][C@:40]([CH2:45][C:46]#[N:47])([OH:44])[CH2:39]2)[C:34]([F:48])=[CH:33][N:32]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(COC)OC.[Pd]>[F:48][C:34]1[C:35]([NH:37][C@H:38]2[CH2:43][CH2:42][CH2:41][C@:40]([CH2:45][C:46]#[N:47])([OH:44])[CH2:39]2)=[N:36][C:31]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[N:8]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)(=[O:21])=[O:22])[CH:9]=2)=[N:32][CH:33]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 866674512-((1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclohexyl)-ethanenitrile2×

Product 1

HCID 680083052-((1S,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-1-hydroxycyclohexyl)ethanenitrile

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 44a, (0.23 g, 0.55 mmol), 2-((1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclohexyl)-ethanenitrile, 69a, (0.14 g, 0.50 mmol) and Na2CO3 (0.75 mL of 2M solution, 1.50 mmol) in dimethoxyethane (15 mL) was degassed with nitrogen for 30 min. To the reaction mixture was added palladium; triphenylphosphane (0.03 g, 0.03 mmol) and continued to degas the solution for 15 min. The reaction mixture was heated at 120° C. in a pressure tube for 45 min. The reaction mixture was filtered through celite and the filtrate was removed under reduced pressure. The resulting residue was purified by silica gel chromatography (40% EtOAc/Hexanes) to afford 150 mg of desired product: LCMS RT=3.55 (M+H) 539.42.

Workup

  1. customto degas the solution for 15 min
  2. filtrationThe reaction mixture was filtered through celite
  3. customthe filtrate was removed under reduced pressure
  4. customThe resulting residue was purified by silica gel chromatography (40% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-71acb978b30a4b4fa06deb5a9904d0a4
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Linked notes

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