2-Methylpentane → 2-Butan-2-yl-10-chloro-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one

HRID 2234393Notes

Reaction equation

HRID 2234393 reaction equation
Br[C:2]1[C:3]([N:9]([CH:16]([CH2:18][CH3:19])[CH3:17])[CH2:10][CH2:11][C:12]([NH:14][CH3:15])=[O:13])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCCC(C)C>O1CCOCC1.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:17][CH:16]([N:9]1[CH2:10][CH2:11][C:12](=[O:13])[N:14]([CH3:15])[C:2]2[C:3]1=[N:4][C:5]([Cl:8])=[N:6][CH:7]=2)[CH2:18][CH3:19]

Participants

8

Reactant 4

HCID 78922-MethylpentaneHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866175713-[(5-bromo-2-chloro-pyrimidin-4-yl)-butan-2-yl-amino]-N-methyl-propanamide2×

Product 1

HCID 866175702-Butan-2-yl-10-chloro-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-[(5-bromo-2-chloro-pyrimidin-4-yl)-butan-2-yl-amino]-N-methyl-propanamide (Intermediate 88; 559 mg, 1.60 mmol) in anhydrous 1,4-dioxane (15 mL) was added Caesium Carbonate (1.04 g, 3.19 mmol). Nitrogen was bubbled through the reaction mixture for 10 minutes, prior to addition of Tris(dibenzylideneacetone)dipalladium(0) (87 mg, 0.095 mmol) and XANTPHOS (88 mg, 0.152 mmol). The reaction was heated to 100° C. and stirred under nitrogen m for 18 hrs. The reaction mixture was cooled and diluted to ˜40 ml with DCM. The reaction mixture was filtered to remove insoluble material, washing filter cake through with DCM. The filtrate was evaporated to give a brown gum which was purified by flash chromatography on silica (40 g cartridge; ISCO companion) eluting with a 25-75% gradient of ethyl acetate in iso-hexane. Product containing fractions were combined and evaporated to give a waxy off white solid which was trituration with hot iso-hexane afforded, on cooling, and collection by suction filtration the title compound as a pale yellow solid (121 mg, 28%)

Workup

  1. customNitrogen was bubbled through the reaction mixture for 10 minutes
  2. temperatureThe reaction mixture was cooled
  3. filtrationThe reaction mixture was filtered
  4. customto remove insoluble material
  5. washwashing
  6. filtrationfilter cake through with DCM
  7. customThe filtrate was evaporated
  8. customto give a brown gum which
  9. customwas purified by flash chromatography on silica (40 g cartridge; ISCO companion)
  10. washeluting with a 25-75% gradient of ethyl acetate in iso-hexane
  11. additionProduct containing fractions
  12. customevaporated
  13. customto give a waxy off white solid which
  14. customafforded
  15. temperatureon cooling
  16. customcollection
  17. filtrationby suction filtration the title compound as a pale yellow solid (121 mg, 28%)

Sources & evidence

ORD record
ord-b7d02f65fb604d72b1f113429edefcc9
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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