Morpholine → N-(3,4-Difluorobenzyl)-2-isopropyl-6-morpholino-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

HRID 40160

반응식

HRID 40160 반응식
FC(F)(F)S(O[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:26](=[O:37])[NH:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=3)=[C:12]([CH:23]([CH3:25])[CH3:24])[N:13]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:9][CH:8]=1)(=O)=O.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.[Li]N([Si](C)(C)C)[Si](C)(C)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1(C)C=CC=CC=1.CCOC(C)=O.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]>[F:36][C:31]1[CH:30]=[C:29]([CH:34]=[CH:33][C:32]=1[F:35])[CH2:28][NH:27][C:26]([C:11]1[C:10]2[C:14](=[CH:15][C:7]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[CH:8][CH:9]=2)[N:13]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:12]=1[CH:23]([CH3:24])[CH3:25])=[O:37]

참가 물질

8

반응물 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866216073-(3,4-Difluorobenzylcarbamoyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indol-6-yl trifluoromethanesulfonate2회HCID 178418261HCID 178418261, 화합물

생성물 1

HCID 59762287N-(3,4-Difluorobenzyl)-2-isopropyl-6-morpholino-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
110 °C

실험 절차

To a solution of 3-(3,4-difluorobenzylcarbamoyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indol-6-yl trifluoromethanesulfonate (Compound 202, 100 mg, 0.18 mmol) in toluene (10 ml) at 25° C., bubbled with argon then added morpholine (22 mg, 0.25 mmol), LiN(TMS)2 (1M in THF, 0.37 ml, 0.40 mmol), Pd2 (dba)3 (3.2 mg, 0.0035 mmol), and X-Phos (4 mg, 0.011 mmol). The reaction was stirred for 12 h at 110° C., diluted with EtOAc, the organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound as a light brown solid.

후처리

  1. washthe organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes)

출처 및 근거

ORD 기록
ord-d6d15a728d194b5185c373c04264493d
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524917B2

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