2-MERCAPTO-N-METHYLBENZAMIDE → HCID 178485312, compound

HRID 1767162Notes

Reaction equation

HRID 1767162 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7](I)=[CH:8][CH:9]=2)[NH:4][N:3]=1.[SH:12][C:13]1[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=1[C:15]([NH:17][CH3:18])=[O:16]>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].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.CN(C=O)C>[I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([S:12][C:13]3[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=3[C:15]([NH:17][CH3:18])=[O:16])=[CH:8][CH:9]=2)[NH:4][N:3]=1

Participants

6

Reactant 2

HCID 45256012-MERCAPTO-N-METHYLBENZAMIDEHCID 178506533HCID 178506533, compound

Product 1

HCID 178485312HCID 178485312, compoundYield 78.1%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

3,6-diiodoindazole (250.00 g), 2-mercapto-N-methylbenzamide (118.48 g), Pd2(dba)3 (9.28 g), Xantphos (11.73 g), DMF (2.5 L, 10 mL/g), followed by CsOH were added sequentially to a 5 L four-neck flask equipped with a mechanical stirrer and a temperature probe. The reaction mixture was then stirred. The dark mixture was degassed three times by alternately connecting to house vacuum and then nitrogen. The mixture was heated to 70° C. over a period of 30 minutes and maintained at the same temperature for fours, at which time HPLC of the aliquot indicated that the 3,6-diiodoindazole was less than 3%. After cooling, the mixture was poured into a mixture of 7.5 L of water, 1.25 L of toluene and 1.25 L of CH2Cl2 in a 22 L extractor. The mixture was allowed to stir at ambient temperature overnight. A thick precipitate formed overnight. The mixture was filtered and the cake was sucked dry. The cake was further dried at 35° C. under house vacuum for six hours to afford 216 g of the final product. The mother liquor was then extracted with 1.5 L of EtOAc. After partitioning, the aqueous layer was discarded. The organic layer was washed twice each with 2 L of water and concentrated. The residue was treated with 250 mL of CH2Cl2 and stored overnight. A thick precipitate formed overnight. The mixture was filtered and the cake was sucked dry. The cake was dried at 35° C. under house vacuum overnight to afford 24.71 g of the final product. The combined yield was 241 g of the final product. The material showed satisfactory purity and was used in the next step without further purification.

Workup

  1. additionwere added sequentially to a 5 L four-neck flask
  2. customequipped with a mechanical stirrer
  3. customThe dark mixture was degassed three times
  4. temperaturemaintained at the same temperature for fours, at which time HPLC of the aliquot
  5. temperatureAfter cooling
  6. additionthe mixture was poured into a mixture of 7.5 L of water, 1.25 L of toluene and 1.25 L of CH2Cl2 in a 22 L extractor
  7. stirringto stir at ambient temperature overnight
  8. customA thick precipitate formed overnight
  9. filtrationThe mixture was filtered
  10. customthe cake was sucked dry
  11. customThe cake was further dried at 35° C. under house vacuum for six hours

Sources & evidence

ORD record
ord-7376f424d4fb435c856cd812495001a6
Source dataset
uspto-grants-2007_06
Patent number
US07232910B2

Reaction notes

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