1-Hydroxybenzotriazole → HCID 86592879, compound

HRID 1176933Notes

Reaction equation

HRID 1176933 reaction equation
[OH:1][CH2:2][CH2:3][O:4][NH:5][C:6]([C:8]1[C:17]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][C:20]=2[Cl:26])=[C:16]([F:27])[C:11]2[N:12]=[CH:13][N:14]([CH3:15])[C:10]=2[CH:9]=1)=[O:7].[C:28]([NH:35][C@H:36]([C:40](O)=[O:41])[CH:37]([CH3:39])[CH3:38])([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>O.CC(N(C)C)=O>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:17]2[C:8]([C:6]([NH:5][O:4][CH2:3][CH2:2][O:1][C:40](=[O:41])[CH:36]([NH:35][C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH:37]([CH3:39])[CH3:38])=[O:7])=[CH:9][C:10]3[N:14]([CH3:15])[CH:13]=[N:12][C:11]=3[C:16]=2[F:27])=[C:20]([Cl:26])[CH:21]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 83693Boc-L-ValineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10127622Selumetinib

Product 1

HCID 86592879HCID 86592879, compoundYield 46.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

Dimethylacetamide (30 mL) was added to a mixture of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide (3 g, 6.555 mmol), BOC-L-valine (1.710 g, 7.866 mmol), HOBT.H2O (1.004 g, 6.555 mmol) and, TEA (0.929 g, 9.177 mmol) in a 500 mL RBF with a magnetic stirrer and nitrogen line. After 5 minutes, EDCl (1.759 g, 9.177 mmol) saw added to the brown solution in the 500 mL RBF. The mixture was stirred overnight at room temperature. The reaction mixture was added slowly to 210 mL of deionozied water with mechanical stirring. The white slurry was stirred for 1 hour, filtered through a medium fritted funnel. The cake was washed with about 100 mL of water and pulled air through the cake for 10-15 minutes. Tert-butyl methyl ether (70 mL) saw added to the cake and stirred with a spatula. The vacuum filtration was continued. The solids were dried under vacuum at 50° C. to give 2 g of the product containing about 80% of the undesired isomer. The t-butyl methyl ether layer was concentrated to a foam (2.18 g) enriched in the desired product comprising a mixture of isomers.

Workup

  1. stirringThe white slurry was stirred for 1 hour
  2. filtrationfiltered through a medium fritted funnel
  3. washThe cake was washed with about 100 mL of water
  4. customfor 10-15 minutes
  5. additionTert-butyl methyl ether (70 mL) saw added to the cake
  6. stirringstirred with a spatula
  7. filtrationThe vacuum filtration
  8. customThe solids were dried under vacuum at 50° C.

Sources & evidence

ORD record
ord-65a85621a83d4393a2408cbca4c0d1cf
Source dataset
uspto-grants-2010_11
Patent number
US07842816B2

Reaction notes

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