Nitrogen → HCID 9822422, compound

HRID 2268860Notes

Reaction equation

HRID 2268860 reaction equation
N#N.Br[C:4]1[S:5][CH:6]=[CH:7][N:8]=1.Br[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([CH2:22][C:23]2[C:28]([Cl:29])=[CH:27][N:26]=[CH:25][C:24]=2[Cl:30])=[N:12][N:11]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH4+].[Cl-]>C1COCC1.C1(C)C=CC=CC=1.[Zn].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:30][C:24]1[CH:25]=[N:26][CH:27]=[C:28]([Cl:29])[C:23]=1[CH2:22][C:13]1[C:14]2[C:19](=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[C:10]([C:4]2[S:5][CH:6]=[CH:7][N:8]=2)=[N:11][N:12]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 11776Triphenylphosphine2×HCID 25517Ammonium ChlorideHCID 764302-BromothiazoleHCID 9908871HCID 9908871, compound

Product 1

HCID 9822422HCID 9822422, compoundYield 51.6%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 167845palladium(II) acetateCatalyst2×HCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

A suspension of zinc (0.18 g, 2.76 mmoles) in THF/toluene 2:1 (15 ml), under stirring and N2 under reflux, was added with 2-bromothiazole (0.23 ml, 2.5 mmoles). After 2½ hours 4-bromo-1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazine (0.5 g, 1.25 mmoles), prepared as described in example 46, palladium acetate (14 mg, 0.0625 mmole) and triphenylphosphine (32 mg, 0.125 mmole) were added to the cold mixture. The mixture was refluxed for further 30 minutes. After 21 hours the same amounts of palladium acetate and triphenylphosphine were added. After 3 hours under reflux the mixture was cooled and poured into water/ice and NH4Cl, then extracted first with ethyl acetate, then with CH2Cl2. The organic phase was washed with water, anhydrified and concentrated to give a solid which was flash chromatographed (eluent: hexane/ethyl acetate 7:8) to give 0.26 g of the title compound (yield: 51%). m.p.: 225-230° C.

Workup

  1. customprepared
  2. additionwere added to the cold mixture
  3. temperatureThe mixture was refluxed for further 30 minutes
  4. temperatureAfter 3 hours under reflux the mixture
  5. temperaturewas cooled
  6. extractionextracted first with ethyl acetate
  7. washThe organic phase was washed with water, anhydrified
  8. concentrationconcentrated
  9. customto give a solid which
  10. customchromatographed (eluent: hexane/ethyl acetate 7:8)

Sources & evidence

ORD record
ord-357b388424334b31bbbcbc25a86df0e0
Source dataset
uspto-grants-2001_12
Patent number
US06329370B1

Reaction notes

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