Triethylamine → 2-[4-(2,4-difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-9-carboxylic acid

HRID 628066Notes

Reaction equation

HRID 628066 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]4[N:19]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[CH:18]=[N:17][N:16]=4)=[N:8][C:7]=3[C:6]=2[CH:28]=1.CC1(C)C2[C:51](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:50]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(N(CC)CC)C.[C]=[O:79]>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[N:19]1[CH:18]=[N:17][N:16]=[C:15]1[C:9]1[S:10][C:11]2[CH2:12][CH2:13][O:14][C:5]3[CH:4]=[CH:3][C:2]([C:51]([OH:50])=[O:79])=[CH:28][C:6]=3[C:7]=2[N:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57900103HCID 57900103, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 668686062-[4-(2,4-difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-9-carboxylic acid

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Procedure

To a solution of 9-bromo-2-[4-(2,4-difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (250 mg) in methanol (0.50 mL) was added palladium acetate (6 mg), XANTPHOS (31 mg) and triethylamine (2 mL) and the reaction heated at 70° C. under a balloon of carbon monoxide for 16 h. After cooling to room temperature, the mixture was filtered through Celite, washing with ethyl acetate. The filtrate was reduced in vacuo and redissolved in THF (8 mL) and ethanol (4 mL). Sodium hydroxide solution (43 mg in 4 mL of water) was added and the reaction stirred at room temperature for 16 h. The reaction was then acidified with 2 M hydrochloric acid and the resulting solid was filtered and air-dried to give 2-[4-(2,4-difluoro-phenyl)-4H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-9-carboxylic acid.

Workup

  1. filtrationthe mixture was filtered through Celite
  2. washwashing with ethyl acetate
  3. dissolutionredissolved in THF (8 mL)
  4. additionSodium hydroxide solution (43 mg in 4 mL of water) was added
  5. filtrationthe resulting solid was filtered
  6. customair-dried

Sources & evidence

ORD record
ord-674bbb322eb2487382654c32dd3703ba
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

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