Boc-L-Valine → HCID 86592879, 화합물

HRID 1767863노트

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HRID 1767863 반응식
[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.O.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

참가 물질

7

반응물 4

HCID 83693Boc-L-ValineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 10127622Selumetinib

생성물 1

HCID 86592879HCID 86592879, 화합물수율 46.4%

시약·촉매·용매 2

HCID 962Water용매HCID 31374Dimethylacetamide용매

실험 절차

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) was 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) was 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.

후처리

  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) was added to the cake
  6. stirringstirred with a spatula
  7. filtrationThe vacuum filtration
  8. customThe solids were dried under vacuum at 50° C.

출처 및 근거

ORD 기록
ord-cbd3adf2c46843cea8f2ab91098506ee
출처 데이터셋
uspto-grants-2007_06
특허 번호
US07235537B2

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