Nitrogen → HCID 68350442, compound

HRID 877847Notes

Reaction equation

HRID 877847 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@H:11]3[C:15]4([CH2:18][CH2:17][CH2:16]4)[CH2:14][N:13]([C:19]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:20])[CH2:12]3)=[C:8]([C:29](=[O:31])[NH2:30])[CH:7]=[N:6][N:5]2[CH:32]=1.[CH3:33][N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N#N>O1CCOCC1.CCOCC>[C:29]([C:8]1[CH:7]=[N:6][N:5]2[CH:32]=[C:2]([C:37]3[CH:36]=[N:35][N:34]([CH3:33])[CH:38]=3)[CH:3]=[C:4]2[C:9]=1[NH:10][C@H:11]1[C:15]2([CH2:18][CH2:17][CH2:16]2)[CH2:14][N:13]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:12]1)(=[O:31])[NH2:30]

Participants

7

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86707913HCID 86707913, compound

Product 1

HCID 68350442HCID 68350442, compoundYield 103.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (S)-benzyl 8-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-6-azaspiro[3.4]octane-6-carboxylate (120.0 mg, 0.241 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (100 mg, 0.482 mmol) in 1,4-dioxane (3.20 mL) and potassium phosphate (2.0M) (0.361 mL, 0.722 mmol) was degassed for several minutes with N2 gas. 1,1′-Bis(diphenylphosphino)ferrocenepalladium(II) dichloride dichloromethane complex (19.81 mg, 0.024 mmol) was added, degassing was continued for 1 more minute, vial was sealed, and the contents were heated @ 110° C. for 45 minutes. HPLC and LC/MS after 30 min indicated that the reaction had essentially proceeded to completion (m/e 500.16, M+H for desired product). After cooling to r. t., the reaction was diluted with EtOAc and water. The layers were separated, the EtOAc layer was washed with water, brine, dried over Na2SO4, and concentrated under vacuum to yield a solid. Trituration with ether yielded 124.4 mg of the title compound as a pale mustard-colored solid. LC/MS: m/e 500.15 (M+H). This material was used in the next step without further purification.

Workup

  1. addition1,1′-Bis(diphenylphosphino)ferrocenepalladium(II) dichloride dichloromethane complex (19.81 mg, 0.024 mmol) was added
  2. customdegassing
  3. customwas sealed
  4. temperatureAfter cooling
  5. addition, the reaction was diluted with EtOAc and water
  6. customThe layers were separated
  7. washthe EtOAc layer was washed with water, brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under vacuum
  10. customto yield a solid

Sources & evidence

ORD record
ord-bd61b41cbab84ad38fbbb12b8b859b8e
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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