1-Chloro-4-iodobenzene → HCID 70979526, compound

HRID 1485472Notes

Reaction equation

HRID 1485472 reaction equation
[F:1][C:2]1[C:12]2[N:11]3[C:13]([CH3:16])=[N:14][N:15]=[C:10]3[CH2:9][CH2:8][NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=1.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CC([O-])(C)C.[Na+]>>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([N:7]2[CH2:8][CH2:9][C:10]3=[N:15][N:14]=[C:13]([CH3:16])[N:11]3[C:12]3[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]2=3)=[CH:20][CH:19]=1

Participants

5

Reactant 4

HCID 125101-Chloro-4-iodobenzeneHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl2×HCID 23676156Sodium t-butoxideHCID 70979775HCID 70979775, compound

Product 1

HCID 70979526HCID 70979526, compoundYield 36%

Conditions

Temperature
90 °C

Procedure

A disposable tube was charged with 10-fluoro-1-methyl-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (22 mg, 0.101 mmol), 1-chloro-4-iodobenzene (31.3 mg, 0.131 mmol), RuPhos precat. (3.67 mg, 5.04 μmol), dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (2.352 mg, 5.04 μmol), sodium 2-methylpropan-2-olate (19.38 mg, 0.202 mmol), and a stirbar before being evacuated and purged with nitrogen three times. Toluene (1 mL, 0.4 M) was added, and the mixture was stirred at 90° C. 6 h. The mixture was cooled, diluted with ethyl acetate, filtered, and concentrated before being purified by silica gel chromatography (eluting with methylene chloride/methanol/1% ammonium hydroxide) and reverse phase HPLC to yield the title compound as a white amorphous solid (0.012 g, 0.036 mmol, 36%).

Workup

  1. custompurged with nitrogen three times
  2. additionToluene (1 mL, 0.4 M) was added
  3. custom6 h
  4. temperatureThe mixture was cooled
  5. additiondiluted with ethyl acetate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custombefore being purified by silica gel chromatography (eluting with methylene chloride/methanol/1% ammonium hydroxide)

Sources & evidence

ORD record
ord-9e7f87f17158430486a2136060545604
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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