Cesium carbonate → Tert-butyl 5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-benzoate

HRID 2234487Notes

Reaction equation

HRID 2234487 reaction equation
[C:1]([O:5][C:6](=[O:16])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([NH2:14])=[CH:9][C:8]=1[F:15])([CH3:4])([CH3:3])[CH3:2].Cl[C:18]1[N:28]=[C:27]2[C:21]([NH:22][C:23](=[O:36])[C:24](CC)(CC)[CH2:25][N:26]2[CH:29]([CH3:31])[CH3:30])=[CH:20][N:19]=1.[CH3:37][C:38]1(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.[C:79](=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Pd+2].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:13][C:11]1[C:10]([NH:14][C:18]2[N:28]=[C:27]3[C:21]([N:22]([CH3:79])[C:23](=[O:36])[CH2:24][CH2:25][N:26]3[CH:29]3[CH2:30][CH2:38][CH2:37][CH2:31]3)=[CH:20][N:19]=2)=[CH:9][C:8]([F:15])=[C:7]([CH:12]=1)[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:16]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 68684306Tert-butyl 4-amino-5-chloro-2-fluorobenzoate2×HCID 8661758510-Chloro-4,4-diethyl-2-propan-2-yl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2×

Product 1

HCID 68684234Tert-butyl 5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-benzoateYield 918.4%

Reagents, catalysts & solvents 2

HCID 9897284tris(dibenzylideneacetone) palladium (II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-Amino-5-chloro-2-fluorobenzoic acid tert-butyl ester (Intermediate 177; 123 mg, 0.5 mmol) was dissolved in dioxane (7.5 mL). 10-Chloro-2-cyclopentyl-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-8,10,12-trien-5-one (Intermediate 1; 155 mg, 0.55 mmol), XANTPHOS (27 mg, 0.05 mmol) and caesium carbonate (327 mg, 1.0 mmol) were added. The system was purged with a stream of nitrogen for 15 minutes and then tris(dibenzylideneacetone) palladium (II) (28 mg, 0.03 mmol) added. The apparatus was evacuated and backfilled with nitrogen (×3) and then heated at 100° C. for 3 hours. The mixture was cooled, filtered and the filtrate absorbed on to an SCX column, which was subsequently washed with methanol and eluted with ammonia in methanol. Product containing fractions were evaporated and the residue purified by column chromatography (2% MeOH/DCM) to yield the title compound as a pale yellow foam (225 mg, 92%).

Workup

  1. customThe system was purged with a stream of nitrogen for 15 minutes
  2. customThe apparatus was evacuated
  3. temperatureThe mixture was cooled
  4. filtrationfiltered
  5. customthe filtrate absorbed on to an SCX column, which
  6. washwas subsequently washed with methanol
  7. washeluted with ammonia in methanol
  8. additionProduct containing fractions
  9. customwere evaporated
  10. customthe residue purified by column chromatography (2% MeOH/DCM)

Sources & evidence

ORD record
ord-8abe3bea61264e68a6ebf83987ed035c
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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