1,2-Dimethoxyethane → (2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanol

HRID 74941Notes

Reaction equation

HRID 74941 reaction equation
[Cl: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]2C[CH2:42][CH2:41][C:40](C)(O)[CH2:39]2)[C:34]([F:46])=[CH:33][N:32]=1.[C:47]([O-:50])([O-])=O.[Na+].[Na+].[CH2:53](COC)OC>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:31]3[N:36]=[C:35]([NH:37][CH:38]4[CH2:39][CH2:40][CH2:41][CH2:42][C:47]4([CH3:53])[OH:50])[C:34]([F:46])=[CH:33][N:32]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:21])=[O:22])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 86667419(3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanol

Product 1

HCID 67285725(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanol

Conditions

Temperature
130 °C

Procedure

Degassed a solution of 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (1.46 g, 3.37 mmol), (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-1-methyl-cyclohexanol, 29c, (0.72 g, 2.81 mmol) and Na2CO3 (4.21 mL of 2M solution, 8.433 mmol) in dimethoxyethane (15 mL) for 30 min with nitrogen. To the reaction mixture was added palladium tetrakis-triphenylphosphane (0.16 g, 0.14 mmol). The reaction mixture was heated at 130° C. in Q-tube apparatus for 45 minutes. The reaction mixture was filtered through a pad of 1 cm of silica gel and 2 cm celite. The product was purified by silica gel chromatography (hexanes/EtOAc) to afford the desired product, 29e (63% yield).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of 1 cm of silica gel and 2 cm celite
  2. customThe product was purified by silica gel chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-91cf2116bb8142e194364d87426c5bf3
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

Loading…