Tert-butyl cis-(3-carbamoylcyclohexyl)carbamate → tert-butyl N-[(1R,3S)-3-[[4-(5,5-dimethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyridin-3-yl)-5-fluoro-2-pyridinyl]carbamoyl]cyclohexyl]carbamate

HRID 565

Reaction equation

HRID 565 reaction equation
CC(C)(C)OC(=O)N[C@@H]1CCC[C@H](C(N)=O)C1.CC1(C)CCn2ncc(-c3cc(Cl)ncc3F)c2C1>C1COCCO1.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(P(c2ccccc2)c2ccccc2)cc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1.c1ccc(P(c2ccccc2)c2ccccc2)cc1>CC1(C)CCn2ncc(-c3cc(NC(=O)[C@H]4CCC[C@@H](NC(=O)OC(C)(C)C)C4)ncc3F)c2C1

Participants

7

Reactant 2

HCID 71279992Tert-butyl cis-(3-carbamoylcyclohexyl)carbamateHCID 1241551563-(2-chloro-5-fluoro-4-pyridinyl)-5,5-dimethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyridine

Product 1

HCID 124164049tert-butyl N-[(1R,3S)-3-[[4-(5,5-dimethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyridin-3-yl)-5-fluoro-2-pyridinyl]carbamoyl]cyclohexyl]carbamateYield 52.81%

Reagents, catalysts & solvents 4

HCID 10796Cesium carbonateReagentHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (0.496 g, 0.43 mmol) was added to 3-(2-chloro-5-fluoropyridin-4-yl)-5,5-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (1.2g, 4.29 mmol), tert-butyl ((1R,3S)-3-carbamoylcyclohexyl)carbamate (1.039 g, 4.29 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.496 g, 0.86 mmol) and Cesium carbonate (4.19 g, 12.87 mmol) in 1,4-dioxane (10 mL)Degassed for 5 mins under nitrogen and the resulting suspension was stirred at 120 °C for 17 hours in the microwave reactor. The reaction mixture was partitioned between water (20ml) and ethyl acetate (100ml) filtered and separated. The organics were absorbed onto silica and purified by flash silica chromatography, elution gradient 1:1 EtOAc in heptane. Pure fractions were evaporated to dryness to afford tert-butyl ((1R,3S)-3-((4-(5,5-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-5-fluoropyridin-2-yl)carbamoyl)cyclohexyl)carbamate (1.100 g, 52.8 %) as a white solid.

Sources & evidence

ORD record
ord-6e943c9408c04e8290b1b5ad8908a7f2
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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